This article was downloaded by: [University of Exeter] On: 03 August 2015, At: 03:27 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: 5 Howick Place, London, SW1P 1WG
The American Journal of Drug and Alcohol Abuse Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/iada20
The impact of posttraumatic stress disorder on cannabis quit success Marcel O. Bonn-Miller PhD e
abcd
bf
b
, Rudolf H. Moos PhD , Matthew Tyler Boden PhD , W. Robert a
Long MSc , Rachel Kimerling PhD & Jodie A. Trafton PhD
bf
a
National Center for PTSD, VA Palo Alto Health Care System, CA, USA,
b
Center for Innovation to Implementation, VA Palo Alto Health Care System, CA, USA,
c
Center of Excellence in Substance Abuse Treatment and Education, Philadelphia VAMC, PA, USA, d
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, PA, USA,
Click for updates
e
Centre for Epidemiology and Biostatistics, University of Leeds, UK, and
f
Department of Psychiatry and Behavioral Sciences, Stanford University, CA, USA Published online: 25 Jul 2015.
To cite this article: Marcel O. Bonn-Miller PhD, Rudolf H. Moos PhD, Matthew Tyler Boden PhD, W. Robert Long MSc, Rachel Kimerling PhD & Jodie A. Trafton PhD (2015) The impact of posttraumatic stress disorder on cannabis quit success, The American Journal of Drug and Alcohol Abuse, 41:4, 339-344, DOI: 10.3109/00952990.2015.1043209 To link to this article: http://dx.doi.org/10.3109/00952990.2015.1043209
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
http://informahealthcare.com/ada ISSN: 0095-2990 (print), 1097-9891 (electronic) Am J Drug Alcohol Abuse, 2015; 41(4): 339–344 ! 2015 Informa Healthcare USA, Inc. DOI: 10.3109/00952990.2015.1043209
ORIGINAL ARTICLE
The impact of posttraumatic stress disorder on cannabis quit success Marcel O. Bonn-Miller, PhD1,2,3,4, Rudolf H. Moos, PhD2,6, Matthew Tyler Boden, PhD2, W. Robert Long, MSc5, Rachel Kimerling, PhD1, and Jodie A. Trafton, PhD2,6 National Center for PTSD, VA Palo Alto Health Care System, CA, USA, 2Center for Innovation to Implementation, VA Palo Alto Health Care System, CA, USA, 3Center of Excellence in Substance Abuse Treatment and Education, Philadelphia VAMC, PA, USA, 4Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, PA, USA, 5Centre for Epidemiology and Biostatistics, University of Leeds, UK, and 6Department of Psychiatry and Behavioral Sciences, Stanford University, CA, USA
Downloaded by [University of Exeter] at 03:27 03 August 2015
1
Abstract
Keywords
Background: Though a growing number of US Veterans are being diagnosed with cannabis use disorders, with posttraumatic stress disorder (PTSD) observed as the most frequently co-occurring psychiatric disorder among this population, no research has investigated the impact of PTSD diagnosis on cannabis quit success. Objectives: The present study sought to determine the impact of PTSD on cannabis use following a self-guided quit attempt. Methods: Participants included 104, primarily male, cannabis-dependent US Veterans (Mage ¼ 50.90 years, SDage ¼ 9.90). The study design was prospective and included an assessment immediately prior to the quit attempt, and assessments weekly for the first 4 weeks post-quit, and then monthly through 6 months post-quit. Results: Results indicated that PTSD diagnosis was not associated with time to first lapse or relapse. However, individuals with PTSD used more cannabis at baseline and evidenced a slower initial decline in cannabis use immediately following the quit attempt. All findings were significant after accounting for alcohol and tobacco use across the cessation period, as well as co-occurring mood and anxiety disorder diagnoses. Conclusion: Findings highlight the potential utility of interventions for individuals with cannabis use disorder and co-occurring PTSD, particularly early in a cessation attempt.
Cannabis, cessation, marijuana, posttraumatic stress disorder (PTSD)
Introduction Cannabis is the most widely used illicit drug in the United States and rates of cannabis use disorder diagnoses among Veterans have increased over 50% in the past decade (1,2). In part, these increased rates among Veterans may be attributed to increases in the prevalence of posttraumatic stress disorder (PTSD) (3). Indeed, exposure to trauma has been associated with higher rates of cannabis use, and cannabis use disorders now represent the most prevalent illicit substance use disorders among Veterans with PTSD (4–7). Furthermore, PTSD is one of the most prevalent psychiatric disorders among Veterans with cannabis use disorders; approximately 30% of Veterans with cannabis use disorders, and no co-occurring illicit substance use disorders, have a diagnosis of PTSD (1). Given the co-occurrence between cannabis and PTSD, it is striking how little work has been conducted to understand their interrelations, particularly among military Veterans.
Address correspondence to Marcel O. Bonn-Miller, 795 Willow Road (152-MPD), Menlo Park, CA 94025, USA. E-mail: [email protected]
History Received 10 November 2014 Revised 17 March 2015 Accepted 17 March 2015 Published online 4 June 2015
In addition to recent work documenting the prevalence of PTSD among medical cannabis treatment seekers and regular users (8,9), prior studies have shown that PTSD (and greater PTSD symptomatology) is associated with greater odds of cannabis use (10), frequency of use (4), frequency of use following residential PTSD treatment (11), coping-oriented use motives among sub-clinical samples (12), coping-oriented use motives, problems associated with use, and craving immediately prior to a cannabis quit attempt (13), and severity of withdrawal symptoms during a cannabis quit attempt (13). Furthermore, individuals with a cannabis use disorder who discontinue use in order to receive PTSD treatment have poorer PTSD treatment outcomes than those without a cannabis use disorder (14). These findings indicate that individuals with PTSD use cannabis at a high frequency and for coping reasons, have greater problems associated with use, and experience greater withdrawal and craving during a quit attempt. Therefore, it is likely that individuals with PTSD who are cannabis-dependent have difficulty cutting down or abstaining from cannabis use. Though no such examination has been conducted to date, individuals with co-occurring PTSD and other substance use disorders have more difficulty abstaining from substance use than their non-PTSD counterparts (15–17). Indeed, PTSD has
Downloaded by [University of Exeter] at 03:27 03 August 2015
340
M. O. Bonn-Miller et al.
Am J Drug Alcohol Abuse, 2015; 41(4): 339–344
been associated with greater rates of lapse (slip or violation of the abstinence goal) (18) and relapse (return to previous level of use, abandonment of abstinence goal) (18) to substance use following a quit attempt, as well as greater frequency of substance use post-quit (19,20). The present study aimed to examine the connection between PTSD and lapse (i.e. cannabis use), relapse (i.e. use on 4 of 7 consecutive days) (21,22), and frequency of use following a self-guided quit attempt among dependent cannabis users. We focused on individuals attempting a self-guided cessation attempt because the majority of cannabis-dependent individuals try to quit on their own rather than seek professional assistance (23). Military Veterans were chosen as the focus of the study as they have some of the highest rates of PTSD, as well as increasing rates of cannabis use disorders (1,24–26). Finally, we chose a 6-month window to observe the hypothesized effects as prior work indicates that this window is ample to observe the majority of lapses and relapses that occur postcannabis-cessation (22,27). We had two hypotheses: (i) we expected that, following a self-guided quit attempt, cannabisdependent individuals with PTSD would lapse and relapse to cannabis more quickly than their non-PTSD counterparts, and (ii) we expected that PTSD would change the trajectory of cannabis use following a self-guided quit attempt, such that individuals with PTSD would use cannabis more frequently and take longer to reduce their overall use than their non-PTSD counterparts.
PTSD Scale (28), 26 participants met DSM-IV (29) criteria for PTSD, while 78 participants did not. The majority of participants who did not meet criteria for PTSD were not exposed to trauma (50/78; 64.1%). Participants with and without co-occurring PTSD did not significantly differ in terms of age, gender, or education status (p’s40.16), but did differ in terms of race/ethnicity (2 (5) ¼ 16.17, p ¼ 0.006). Individuals with PTSD were more likely to be Hispanic (36.0% vs. 6.5%), while individuals without PTSD were more likely to be White/Caucasian (39.0% vs. 28.0%) or Black/ Non-Hispanic (41.6% vs. 20.0%). The majority of the participants (94.2%) had a current diagnosis of abuse or dependence of a substance other than cannabis (i.e. alcohol, opiates, sedative/hypnotics, cocaine, amphetamines, hallucinogens, inhalants). Additionally, 35.6% met criteria for a current anxiety disorder other than PTSD (i.e. panic disorder, generalized anxiety disorder, obsessive compulsive disorder, phobia [specific, agoraphobia, social]), and 42.3% met criteria for a current mood disorder (i.e. major depressive disorder, bipolar I/II disorder, dysthymia). Participants with co-occurring PTSD were significantly more likely to have an additional mood (2 (1) ¼ 11.77, p ¼ 0.001) or anxiety (2 (1) ¼ 8.92, p ¼ 0.003) disorder than participants without PTSD, but participants with and without PTSD were equally likely to have an additional substance-use disorder (2 (1) ¼ 2.23, p ¼ 0.14).
Methods
Psychiatric diagnoses
Participants
Prevalence of current Axis-I diagnoses, including cannabis dependence1 but excluding PTSD, was determined by the Structured Clinical Interview-Non-Patient Version for DSMIV (SCID-I-N/P) (30). The Clinician-Administered PTSD Scale (CAPS) (28) was used to assess the intensity and frequency of DSM-IV PTSD symptoms, and thus identify individuals meeting criteria for PTSD. Consistent with wellestablished diagnostic guidelines (31), participants were scored positive for a symptom when the intensity score was greater than or equal to one and the frequency score was greater than or equal to 2. Individuals were designated as meeting criteria for PTSD when they: (a) met DSM-IV diagnostic criteria A, (b) met diagnostic criteria for each of the three symptom clusters, and (c) obtained a CAPS severity score (i.e. frequency + intensity) of 45 or higher (32). The SCID-I-N/P and CAPS were administered by trained research assistants and all interviews were audio-recorded and diagnoses were confirmed by the first author following a review of recorded interviews.
Inclusion criteria were (i) being a US military Veteran, (ii) meeting diagnostic criteria for current cannabis dependence*, (iii) reporting a current level of motivation to quit of at least 5 on a 10 point scale (0 ¼ ‘‘no interest in quitting’’ to 10 ¼ ‘‘definite interest in quitting’’), and (iv) being interested in making a serious self-guided quit attempt. Exclusion criteria included (a) limited mental competency and inability to give informed, voluntary, written consent, (b) a significant change (decrease of425%) in amount of cannabis smoked per day during the previous month, (c) pregnancy or current breastfeeding, and (d) current suicidal ideation. A total of 107 participants met eligibility criteria. Three participants did not complete any of the listed measures and were thus excluded from analyses. Thus, participants were 104 cannabis-dependent military Veterans (95.2% male; Mage ¼ 50.90 years, SDage ¼ 9.90). These individuals reported their race/ethnicity as White/Caucasian (36.3%) or Black//Non-Hispanic (36.3%), Hispanic (13.7%), ‘‘Other’’ (11.8%), Black/Hispanic (1.0%), or Asian (1.0%). The majority of participants completed high school (93.2%), and 36.9% of participants graduated from a 2or 4-year college. Participants with co-occurring PTSD were actively recruited. As identified using the Clinician-Administered
*Diagnostic criteria for cannabis dependence were consistent with the definition set forth in the DSM-IV-TR (29), with the addition of withdrawal, consistent with DSM-5 (49).
Measures
Substance use and lapse/relapse The timeline follow-back (TLFB) procedure (33) was used to assess self-reported use of cannabis, as well as alcohol and tobacco. The TLFB was administered at baseline to determine mean cannabis, alcohol, and tobacco used on each day for the prior 90 days, and at each time-point post-quit to obtain substance use information following the cessation attempt. Quantity of cannabis used on each day was indexed by a graphical depiction that ranged from 0–8 (34).
Impact of PTSD on cannabis
DOI: 10.3109/00952990.2015.1043209
Downloaded by [University of Exeter] at 03:27 03 August 2015
Procedure Interested persons, responding to flyers posted throughout a VA Medical Center, contacted the research team and were provided with a description of the study via phone. Participants were initially screened for eligibility, and those eligible scheduled for a baseline appointment. Participants were instructed to schedule their appointment 1-day prior to the day that they would be willing to make a serious cannabis quit attempt. Upon arrival to the laboratory, each participant provided written consent to participate in the study. Next, participants were administered the SCID I-N/P (30) and CAPS (28) by trained interviewers to assess key exclusionary and inclusionary criteria. If deemed eligible, participants then completed the TLFB (33). At the conclusion of this appointment, participants were compensated $75 and instructed to make a serious quit attempt starting the morning of the following day. Participants returned to the lab at 1, 2, 3, and 4 weeks as well as 2, 3, 4, 5, and 6 months following the initiation of their quit attempt. At each follow-up, participants completed the TLFB and were compensated $15. All study procedures were approved by the VA and Stanford University Institutional Review Boards (IRBs). A Certificate of Confidentiality was also obtained from the National Institutes on Drug Abuse (NIDA) to protect participants in the reporting of their substance use behaviors.
Results The number of participants who provided data at each timepoint was: 94 (90.4% of total sample) at Week 1, 85 (81.7%) at Week 2, 83 (79.8%) at Week 3, 80 (76.9%) at Week 4, 78 (75.0%) at Month 2, 75 (72.1%) at Month 3, 74 (71.2%) at Month 4, 67 (64.4%) at Month 5 and 65 (62.5%) at Month 6. The percentage of participants providing data significantly differed at each time-point depending on PTSD diagnosis (2 (1, n ¼ 104) ¼ 6.20–14.05, ps50.05), with 18–37% more participants without a PTSD diagnoses providing data. We note that variation in sample size by analysis is due to different patterns of missing TLFB data. Descriptive statistics for mean cannabis, alcohol, and tobacco use at all time-points are shown in Table 1. Demonstrating the commitment of participants to quit using cannabis, repeated measures ANOVA analyses revealed that the mean use of cannabis was significantly reduced from baseline to each follow-up (all p50.001, all p2 4 0:59). Nevertheless, a majority of
individuals lapsed (n ¼ 72 out of 78 with data [92.3%]; defined as one or more use of cannabis), and relapsed (n ¼ 57 out of 77 with data [74.0%]; defined as use on 4 of 7 consecutive days), to cannabis use by the end of the cessation period. Primary analyses With a Cox regression, we used PTSD diagnosis to predict time to first lapse and relapse. PTSD diagnosis did not significantly predict time to first lapse (2 (1, n ¼ 75) ¼ 3.67, p ¼ 0.06; b ¼ 0.57, SE ¼ 0.30, p ¼ 0.06; exp[b] ¼ 0.57, CI [95%] ¼ 0.31–1.02). PTSD diagnosis also did not significantly predict time to first relapse (2 (1, n ¼ 74) ¼ 0.93, p ¼ 0.34; b ¼ 0.31, SE ¼ 0.32, p ¼ 0.34; exp[b] ¼ 0.74, CI [95%] ¼ 0.39–1.34). Using generalized linear mixed modeling (GLMM; as implemented by R) (35) we examined the association of PTSD diagnosis and the trajectory of mean cannabis use across the 6 months following the quit attempt (aggregated to nine time-points representing mean use during Weeks 1 through 4 and Months 2 through 6). Between-person parameters were estimated for: (a) the mean cannabis use score at the intercept for participants without PTSD, (b) the association between PTSD diagnosis and mean cannabis use scores at the intercept, (c) the average slope over time, and (d) the association between PTSD diagnosis and cannabis use trajectories. These latter parameters are measures of change per unit time associated with PTSD after accounting for baseline scores and the non-independence of observations. We hypothesized that a quadratic model best accounted for the data, given that cannabis use was likely to substantially decrease following the quit attempt, and then decrease more slowly or level off. Indeed, plotted data representing mean cannabis use for participants with and without PTSD over the cessation period (see Figure 1) supported this hypothesis, as did the better fit statistics of a GLMM including a quadratic slope and linear slope relative to a GLMM including a linear slope only. In our analysis, the intercept was allowed to vary between participants, and the restricted maximum likelihood estimation method and an unstructured covariance specification were used. In terms of the GLMM analysis, cannabis use was observed to significantly decrease in a linear (b ¼ 0.03, SE ¼ 0.04, Z ¼ 7.15, p50.001) and quadratic (b ¼ 0.01,
Table 1. Descriptive statistics. Cannabis use Mean (SD) Baseline Week 1 Week 2 Week 3 Week 4 Month 2 Month 3 Month 4 Month 5 Month 6
5.74 1.88 1.72 1.65 1.60 1.64 1.79 1.56 1.64 1.60
(2.07) (2.22)*** (2.26)*** (2.06)*** (2.06)*** (2.21)*** (2.42)*** (2.39)*** (2.30)*** (2.25)***
Alcohol use Range
1.50–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00
Mean (SD) 2.39 0.64 0.54 0.69 0.62 0.60 0.72 0.66 0.84 0.90
341
(4.98) (2.32)** (1.57)** (2.00)** (1.79)** (1.91)** (1.90)** (1.72)** (2.14)** (2.61)**
Tobacco use Range
0.00–32.52 0.00–20.00 0.00–10.00 0.00–10.86 0.00–10.71 0.00–12.00 0.00–11.00 0.00–9.00 0.00–10.00 0.00–13.46
*p50.05, **p50.01, ***p50.001 for comparisons with baseline value.
Mean (SD) 6.29 4.76 4.67 4.10 4.11 4.45 4.81 4.10 4.03 4.44
(8.01) (6.01)* (6.14) (5.86)* (5.30)* (6.10) (6.60) (6.26)* (6.50)* (6.84)*
Range 0.00–30.22 0.00–20.00 0.00–20.00 0.00–25.00 0.00–17.50 0.00–20.00 0.00–20.00 0.00–20.00 0.00–20.00 0.00–21.00
Mean Cannabis Use
342
M. O. Bonn-Miller et al. 8.00 7.00 6.00 5.00 4.00 3.00 2.00 1.00 .00
Am J Drug Alcohol Abuse, 2015; 41(4): 339–344
No PTSD Diagnosis PTSD Diagnosis
Downloaded by [University of Exeter] at 03:27 03 August 2015
Figure 1. Trajectories of mean cannabis use separately for participants with and without a posttraumatic stress disorder (PTSD) diagnosis.
SE ¼ 0.002, Z ¼ 5.97, p50.001) manner. We estimated mean cannabis use at the intercept among individuals without PTSD at 3.13 (SE ¼ 0.22, Z ¼ 14.23, p50.001). PTSD diagnosis significantly predicted greater mean cannabis use at baseline (b ¼ 1.35, SE ¼ 0.46, Z ¼ 2.95, p ¼ 0.003) and, during the cessation period, PTSD diagnosis significantly predicted the linear trajectory of cannabis use (b ¼ 0.21, SE ¼ 0.09, Z ¼ 2.37, p ¼ 0.02), and the quadratic trajectory of cannabis use at trend levels (b ¼ 0.007, SE ¼ 0.004, Z ¼ 1.71, p ¼ 0.09). In other words, PTSD diagnosis predicted the linear decrease in cannabis use over time, but did not significantly predict the instantaneous decrease in cannabis use after the cessation attempt (i.e. both groups with and without PTSD experienced this instantaneous decrease) (36). This can be seen in Figure 1, in which participants with and without PTSD experience steep initial declines in cannabis use. Participants with PTSD then continue to decline in cannabis use, whereas participants without PTSD tend to remain level in their cannabis use. Subsidiary analyses We conducted two post-hoc analyses to investigate whether observed findings remained after adjusting for (i) average alcohol and tobacco use during the cessation period, and (ii) co-occurring mood and anxiety disorder (other than PTSD) diagnoses. We interpreted results of the latter analysis with caution as individuals with and without PTSD meaningfully vary in terms of co-occurring diagnoses, with no valid statistical method to ‘‘control’’ for this difference (37). Adjusting for average alcohol and tobacco use during the cessation period, PTSD diagnosis continued to significantly predict greater mean cannabis use at baseline (b ¼ 1.31, SE ¼ 0.44, Z ¼ 2.99, p ¼ 0.003), as well as the linear trajectory of cannabis use by PTSD diagnosis (b ¼ 0.21, SE ¼ 0.09, Z ¼ 2.28, p ¼ 0.02), but not the quadratic trajectory of cannabis use (b ¼ 0.007, SE ¼ 0.004, Z ¼ 1.67, p ¼ 0.10). After adjusting for current mood and anxiety disorder diagnoses (other than PTSD), PTSD diagnosis continued to significantly predict greater mean cannabis use at baseline (b ¼ 1.40, SE ¼ 0.49, Z ¼ 2.86, p ¼ 0.004), as well as the linear trajectory of cannabis use by PTSD diagnosis (b ¼ 0.20, SE ¼ 0.10, Z ¼ 2.06, p ¼ 0.04), but not the quadratic trajectory of cannabis use (b ¼ 0.005, SE ¼ 0.003, Z ¼ 1.64, p ¼ 0.10). Thus, results remained similar in size and statistical significance when adjusting for covariates.
Discussion The present study is the first empirical investigation of the association between PTSD and cannabis cessation. Contrary to expectation and prior findings among substance users more broadly (15–17), a diagnosis of PTSD did not increase the risk of either a lapse or relapse to cannabis use following a selfguided cessation attempt. However, partially consistent with expectation and prior work (13), individuals with PTSD were more likely to (i) initially use cannabis at higher rates, and (ii) take longer to reduce their cannabis use at the beginning of the cessation period, than those without PTSD. Though our results also demonstrated a linear decline in cannabis use over the cessation period among those with PTSD, relative to consistent use among individuals without PTSD, it is important to contextualize these differences within the observed disparity in use directly following the quit attempt (see Figure 1). Indeed, as initial reductions in cannabis use were far smaller among participants with PTSD, there was greater room for reductions in use relative to the non-PTSD group later in the cessation period; there were little to no differences observed between groups after the first month of the cessation period. Importantly, post-hoc analyses revealed that the observed differences were between individuals with and without PTSD, and were not a function of alcohol or tobacco use, or co-occurring anxiety and mood disorders, which have independently been associated with cannabis dependence and quit success in prior investigations (38–40). Results from this investigation are consistent with a harmreduction perspective (41) as they show that observed differences were not in relation to abstinence, but rather reductions in use. Indeed, findings highlight the importance of examining multiple indices of substance use, rather than simply lapse and relapse, following a cessation attempt. Results also indicate that the categorical examination of PTSD provides important information in terms of understanding those at risk for poor initial cessation outcomes. The findings have some clinical implications. They suggest that individuals with PTSD have more difficulty initially reducing their cannabis use than individuals without PTSD, though differences between groups may disappear over time. In conjunction with prior empirical work, findings are consistent with a model whereby individuals with PTSD find cannabis to be a useful short-term coping strategy to reduce acute symptoms (e.g. poor sleep) (42). However, coping-oriented use among this population may lead to dependence and exacerbated symptoms of withdrawal and craving during cessation attempts (13,34). As cannabis withdrawal symptoms overlap with PTSD symptoms (43), individuals with PTSD may experience withdrawal as particularly aversive (44) and thus be more apt to continue to use cannabis at higher rates than their non-PTSD counterparts, particularly early during a cessation attempt when withdrawal would likely be most severe for this population (45). This is supported by data from the present study documenting that individuals with PTSD used cannabis at higher rates during the time at which cannabis withdrawal would have been at its worst (i.e. during the first 3 weeks of the quit attempt) (45). Though this model needs further empirical investigation, it appears likely that
Impact of PTSD on cannabis
Downloaded by [University of Exeter] at 03:27 03 August 2015
DOI: 10.3109/00952990.2015.1043209
cannabis-dependent individuals with PTSD may particularly benefit from withdrawal symptom management (e.g. dronabinol, zolpidem) (46,47) as well as specialized treatments that address the functional nature of cannabis use in terms of acute PTSD symptom alleviation. Although the findings are of interest, the present study is not without limitation. First, all assessments were obtained via self-report, and information regarding co-occurring psychosocial treatment receipt and prescription medication use were not collected. Though the self-report limitation is tempered by the use of well-validated ‘‘gold-standard’’ measures, some of which have been shown to be as effective as objective tests (e.g. TLFB) (48), future work would benefit from collecting data on concurrent psychosocial and pharmacological treatment receipt, employing multi-method assessments, particularly for PTSD symptoms, as well as testing of biological specimens (e.g. urine) to confirm self-report cannabis use status. Indeed, though cannabis use/abstinence was not confirmed via testing of biological specimens, as (i) there was no differential reinforcement for abstinence, and (ii) participants were informed that the study investigators received a Certificate of Confidentiality from NIDA, we have confidence in the validity of self-reported cannabis use during the study period. Second, the present study employed DSM-IV (29) criteria for cannabis dependence and PTSD diagnosis due to the timing of the study relative to DSM version. Though the diagnosis of cannabis dependence included withdrawal, as it was known by study investigators at the time of the investigation that this would be added as criteria for diagnosis in DSM-5 (49), given extensive revision to diagnostic criteria for both PTSD and cannabis dependence, future investigations would benefit from employing DSM-5 (49) criteria for PTSD and cannabis use disorder. Third, as the sample was comprised of military Veterans, the majority of whom were male, the generalizability of the findings are somewhat limited. However, the association between cannabis and PTSD has also been observed in epidemiological studies of non-Veteran populations (10), lending support for the applicability of these findings to more general, non-Veteran, populations. That said, future work would benefit from determining whether PTSD diagnosis is related to heightened cannabis use post-cessation attempt among female and non-military samples. Finally, though the present study purposefully recruited individuals who were interested in making a self-guided quit attempt, it is possible that the particularly high rates of lapse and relapse observed among this group may have hindered the ability to detect the effect of PTSD on time to lapse and relapse. Future work would benefit from replicating and extending the current investigation among individuals engaged in formal empirically-supported treatments for cannabis dependence (e.g. contingency management, cognitive-behavioral therapy) (50).
Funding This work was supported by a VA Clinical Science Research and Development (CSR&D) Career Development Award – 2, granted to Dr. Bonn-Miller. The expressed views do not necessarily represent those of the Department of Veterans Affairs.
343
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.
References 1. Bonn-Miller MO, Harris AH, Trafton JA. Prevalence of cannabis use disorder diagnoses among veterans in 2002, 2008, and 2009. Psycholog Services 2012;9:404–416. 2. Substance Abuse and Mental Health Services Administration (SAMHSA). Results from the 2012 National Survey on Drug Use and Health: summary of National Findings. Rockville (MD): SAMHSA; 2013. 3. Institute of Medicine. Treatment for posttraumatic stress disorder in military and veteran populations: final assessment. Washington, DC: Institute of Medicine; 2014. 4. Bremner JD, Southwick SM, Darnell A, Charney DS. Chronic PTSD in Vietnam combat veterans: course of illness and substance abuse. Am J Psychiatry 1996;153:369–375. 5. Kilpatrick DG, Acierno R, Saunders B, Resnick HS, Best CL, Schnurr PP. Risk factors for adolescent substance abuse and dependence: data from a national sample. J Consul Clin Psychol 2000;68:19–30. 6. Vlahov D, Galea S, Resnick H, Ahern J, Boscarino JA, Bucuvalas M, Gold J, et al. Increased use of cigarettes, alcohol, and marijuana among Manhattan, New York, residents after the September 11th terrorist attacks. Am J Epidemiol 2002;155:988–996. 7. Program Evaluation and Resource Center VA; 2014. 8. Bonn-Miller MO, Boden MT, Bucossi MM, Babson KA. Selfreported cannabis use characteristics, patterns and helpfulness among medical cannabis users. Am J Drug Alcohol Abuse 2014;40: 23–30. 9. Bohnert KM, Perron BE, Ashrafioun L, Kleinberg F, Jannausch M, Ilgen MA. Positive posttraumatic stress disorder screens among first-time medical cannabis patients: prevalence and association with other substance use. Addict Behav 2014;39:1414–1417. 10. Cougle JR, Bonn-Miller MO, Vujanovic AA, Zvolensky MJ, Hawkins KA. Posttraumatic stress disorder and cannabis use in a nationally representative sample. Psychol Addictive Behav 2011; 25:554–558. 11. Bonn-Miller MO, Vujanovic AA, Drescher KD. Cannabis use among military veterans after residential treatment for posttraumatic stress disorder. Psychol Addictive Behav 2011;25:485–491. 12. Bonn-Miller MO, Vujanovic AA, Feldner MT, Bernstein A, Zvolensky MJ. Posttraumatic stress symptom severity predicts marijuana use coping motives among traumatic event-exposed marijuana users. J Traumatic Stress 2007;20:577–586. 13. Boden MT, Babson KA, Vujanovic AA, Short NA, Bonn-Miller MO. Posttraumatic stress disorder and cannabis use characteristics among military veterans with cannabis dependence. Am J Addictions/Am Acad Psychiat Alcohol Addict 2013;22:277–284. 14. Bonn-Miller MO, Boden MT, Vujanovic AA, Drescher KD. A prospective investigation of the impact of cannabis use disorders on posttraumatic stress disorder symptoms among veterans in residential treatment. Psycholog Trauma: Theory Res Pract Policy 2013;5:193–200. 15. Ouimette PC, Ahrens C, Moos RH, Finney JW. Posttraumatic stress disorder in substance abuse patients: relationship to 1-year posttreatment outcomes. Psychol Addict Behav 1997;11:34–47. 16. Ouimette PC, Finney JW, Moos RH. Two-year posttreatment functioning and coping of substance abuse patients with posttraumatic stress disorder. Psychol Addict Behav 1999;13:105–114. 17. Read JP, Brown PJ, Kahler CW. Substance use and posttraumatic stress disorders: symptom interplay and effects on outcome. Addict Behav 2004;29:1665–1672. 18. Larimer ME, Palmer RS, Marlatt GA. Relapse prevention. An overview of Marlatt’s cognitive-behavioral model. Alcohol Res Health 1999;23:151–160. 19. Ouimette P, Brown PJ. Trauma and substance abuse: causes, consequences, and treatment of comorbid disorders, 1st ed. Washington, DC: American Psychological Association; 2003. 20. Ouimette PC, Brown PJ, Najavits LM. Course and treatment of patients with both substance use and posttraumatic stress disorders. Addict Behav 1998;23:785–795.
Downloaded by [University of Exeter] at 03:27 03 August 2015
344
M. O. Bonn-Miller et al.
21. Hall SM, Havassy BE, Wasserman DA. Commitment to abstinence and acute stress in relapse to alcohol, opiates, and nicotine. J Consult Clin Psychol 1990;58:175–181. 22. Moore BA, Budney AJ. Relapse in outpatient treatment for marijuana dependence. J Substance Abuse Treat 2003;25:85–89. 23. Cunningham JA. Remissions from drug dependence: is treatment a prerequisite? Drug Alcohol Depend 2000;59:211–213. 24. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:593–602. 25. Seal KH, Metzler TJ, Gima KS, Bertenthal D, Maguen S, Marmar CR. Trends and risk factors for mental health diagnoses among Iraq and Afghanistan veterans using Department of Veterans Affairs health care, 2002–2008. Am J Public Health 2009;99:1651–1658. 26. Weiss DS, Marmar CR, Schlenger WE, Fairbank JA, Jordan BK, Hough RL, Kulka RA. The prevalence of lifetime and partial posttraumatic stress disorder in Vietnam theater veterans. J Traumatic Stress 1992;5:365–376. 27. McRae AL, Budney AJ, Brady KT. Treatment of marijuana dependence: a review of the literature. J Substance Abuse Treat 2003;24:369–376. 28. Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM. The development of a ClinicianAdministered PTSD Scale. J Traumatic Stress 1995;8:75–90. 29. American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders: DSM-IV-TR, 4th ed. Washington, DC: APA; 2000. 30. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV-TR Axis I disorders, Research Version, Non-patient edition. New York: Biometrics Research, New York State Psychiatric Institute; 2002. 31. Weathers FW, Keane TM, Davidson JR. Clinician-administered PTSD scale: a review of the first ten years of research. Depression Anxiety 2001;13:132–156. 32. Weathers FW, Ruscio AM, Keane TM. Psychometric properties of nine scoring rules for the Clinician-Administered Posttraumatic Stress Disorder Scale. Psychological Assess 1999;11:124–133. 33. Sobell L, Sobell M. Timeline follow-back: a technique for assessing self-reported ethanol consumption. In: Allen J, Litten RZ, eds. Measuring alcohol consumption: psychosocial and biological methods; Totowa (NJ): Humana Press; 1992:41–72. 34. Bonn-Miller MO, Zvolensky MJ. An evaluation of the nature of marijuana use and its motives among young adult active users. Am J Addictions/Am Acad Psychiatrists Alcohol Addict 2009;18: 409–416. 35. Ihaka R, Gentleman R. R: a language for data analysis and graphics. J Computat Graphical Stat 1996;5:299–314.
Am J Drug Alcohol Abuse, 2015; 41(4): 339–344
36. Singer JD, Willett JB. Applied longitudinal data analysis: modeling change and event occurrence. Oxford/New York: Oxford University Press; 2003. 37. Miller GA, Chapman JP. Misunderstanding analysis of covariance. J Abnormal Psychol 2001;110:40–48. 38. Rooke SE, Norberg MM, Copeland J. Successful and unsuccessful cannabis quitters: comparing group characteristics and quitting strategies. Subst Abuse Treat, Prevent Policy 2011;6:30. 39. Degenhardt L, Hall W. The relationship between tobacco use, substance-use disorders and mental health: results from the National Survey of Mental Health and Well-being. Nicotine Tobacco Res 2001;3:225–234. 40. Buckner JD, Schmidt NB, Lang AR, Small JW, Schlauch RC, Lewinsohn PM. Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence. J Psychiatric Res 2008; 42:230–239. 41. Marlatt GA. Harm reduction: come as you are. Addict Behav 1996; 21:779–788. 42. Babson KA, Bonn-Miller MO. Sleep disturbances: implications for cannabis use, cannabis use cessation, and cannabis use treatment. Curr Addict Rep 2014;1:109–114. 43. Budney AJ, Hughes JR, Moore BA, Vandrey R. Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry 2004;161:1967–1977. 44. Bonn-Miller MO, Zvolensky MJ, Marshall EC, Bernstein A. Incremental validity of anxiety sensitivity in relation to marijuana withdrawal symptoms. Addict Behav 2007;32:1843–1851. 45. Budney AJ, Moore BA, Vandrey RG, Hughes JR. The time course and significance of cannabis withdrawal. J Abnormal Psychol 2003; 112:393–402. 46. Vandrey R, Smith MT, McCann UD, Budney AJ, Curran EM. Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal. Drug Alcohol Depend 2011;117:38–44. 47. Vandrey R, Stitzer ML, Mintzer MZ, Huestis MA, Murray JA, Lee D. The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users. Drug Alcohol Depend 2013;128: 64–70. 48. Hjorthoj CR, Hjorthoj AR, Nordentoft M. Validity of timeline follow-back for self-reported use of cannabis and other illicit substances – systematic review and meta-analysis. Addict Behav 2012;37:225–233. 49. American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders: DSM-5, 5th ed. Washington, DC: APA; 2013. 50. Roffman RA, Stephens RS. Cannabis dependence: its nature, consequences, and treatment. Cambridge, UK/New York: Cambridge University Press; 2006.
The American Journal of Drug and Alcohol Abuse Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/iada20
The impact of posttraumatic stress disorder on cannabis quit success Marcel O. Bonn-Miller PhD e
abcd
bf
b
, Rudolf H. Moos PhD , Matthew Tyler Boden PhD , W. Robert a
Long MSc , Rachel Kimerling PhD & Jodie A. Trafton PhD
bf
a
National Center for PTSD, VA Palo Alto Health Care System, CA, USA,
b
Center for Innovation to Implementation, VA Palo Alto Health Care System, CA, USA,
c
Center of Excellence in Substance Abuse Treatment and Education, Philadelphia VAMC, PA, USA, d
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, PA, USA,
Click for updates
e
Centre for Epidemiology and Biostatistics, University of Leeds, UK, and
f
Department of Psychiatry and Behavioral Sciences, Stanford University, CA, USA Published online: 25 Jul 2015.
To cite this article: Marcel O. Bonn-Miller PhD, Rudolf H. Moos PhD, Matthew Tyler Boden PhD, W. Robert Long MSc, Rachel Kimerling PhD & Jodie A. Trafton PhD (2015) The impact of posttraumatic stress disorder on cannabis quit success, The American Journal of Drug and Alcohol Abuse, 41:4, 339-344, DOI: 10.3109/00952990.2015.1043209 To link to this article: http://dx.doi.org/10.3109/00952990.2015.1043209
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
http://informahealthcare.com/ada ISSN: 0095-2990 (print), 1097-9891 (electronic) Am J Drug Alcohol Abuse, 2015; 41(4): 339–344 ! 2015 Informa Healthcare USA, Inc. DOI: 10.3109/00952990.2015.1043209
ORIGINAL ARTICLE
The impact of posttraumatic stress disorder on cannabis quit success Marcel O. Bonn-Miller, PhD1,2,3,4, Rudolf H. Moos, PhD2,6, Matthew Tyler Boden, PhD2, W. Robert Long, MSc5, Rachel Kimerling, PhD1, and Jodie A. Trafton, PhD2,6 National Center for PTSD, VA Palo Alto Health Care System, CA, USA, 2Center for Innovation to Implementation, VA Palo Alto Health Care System, CA, USA, 3Center of Excellence in Substance Abuse Treatment and Education, Philadelphia VAMC, PA, USA, 4Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, PA, USA, 5Centre for Epidemiology and Biostatistics, University of Leeds, UK, and 6Department of Psychiatry and Behavioral Sciences, Stanford University, CA, USA
Downloaded by [University of Exeter] at 03:27 03 August 2015
1
Abstract
Keywords
Background: Though a growing number of US Veterans are being diagnosed with cannabis use disorders, with posttraumatic stress disorder (PTSD) observed as the most frequently co-occurring psychiatric disorder among this population, no research has investigated the impact of PTSD diagnosis on cannabis quit success. Objectives: The present study sought to determine the impact of PTSD on cannabis use following a self-guided quit attempt. Methods: Participants included 104, primarily male, cannabis-dependent US Veterans (Mage ¼ 50.90 years, SDage ¼ 9.90). The study design was prospective and included an assessment immediately prior to the quit attempt, and assessments weekly for the first 4 weeks post-quit, and then monthly through 6 months post-quit. Results: Results indicated that PTSD diagnosis was not associated with time to first lapse or relapse. However, individuals with PTSD used more cannabis at baseline and evidenced a slower initial decline in cannabis use immediately following the quit attempt. All findings were significant after accounting for alcohol and tobacco use across the cessation period, as well as co-occurring mood and anxiety disorder diagnoses. Conclusion: Findings highlight the potential utility of interventions for individuals with cannabis use disorder and co-occurring PTSD, particularly early in a cessation attempt.
Cannabis, cessation, marijuana, posttraumatic stress disorder (PTSD)
Introduction Cannabis is the most widely used illicit drug in the United States and rates of cannabis use disorder diagnoses among Veterans have increased over 50% in the past decade (1,2). In part, these increased rates among Veterans may be attributed to increases in the prevalence of posttraumatic stress disorder (PTSD) (3). Indeed, exposure to trauma has been associated with higher rates of cannabis use, and cannabis use disorders now represent the most prevalent illicit substance use disorders among Veterans with PTSD (4–7). Furthermore, PTSD is one of the most prevalent psychiatric disorders among Veterans with cannabis use disorders; approximately 30% of Veterans with cannabis use disorders, and no co-occurring illicit substance use disorders, have a diagnosis of PTSD (1). Given the co-occurrence between cannabis and PTSD, it is striking how little work has been conducted to understand their interrelations, particularly among military Veterans.
Address correspondence to Marcel O. Bonn-Miller, 795 Willow Road (152-MPD), Menlo Park, CA 94025, USA. E-mail: [email protected]
History Received 10 November 2014 Revised 17 March 2015 Accepted 17 March 2015 Published online 4 June 2015
In addition to recent work documenting the prevalence of PTSD among medical cannabis treatment seekers and regular users (8,9), prior studies have shown that PTSD (and greater PTSD symptomatology) is associated with greater odds of cannabis use (10), frequency of use (4), frequency of use following residential PTSD treatment (11), coping-oriented use motives among sub-clinical samples (12), coping-oriented use motives, problems associated with use, and craving immediately prior to a cannabis quit attempt (13), and severity of withdrawal symptoms during a cannabis quit attempt (13). Furthermore, individuals with a cannabis use disorder who discontinue use in order to receive PTSD treatment have poorer PTSD treatment outcomes than those without a cannabis use disorder (14). These findings indicate that individuals with PTSD use cannabis at a high frequency and for coping reasons, have greater problems associated with use, and experience greater withdrawal and craving during a quit attempt. Therefore, it is likely that individuals with PTSD who are cannabis-dependent have difficulty cutting down or abstaining from cannabis use. Though no such examination has been conducted to date, individuals with co-occurring PTSD and other substance use disorders have more difficulty abstaining from substance use than their non-PTSD counterparts (15–17). Indeed, PTSD has
Downloaded by [University of Exeter] at 03:27 03 August 2015
340
M. O. Bonn-Miller et al.
Am J Drug Alcohol Abuse, 2015; 41(4): 339–344
been associated with greater rates of lapse (slip or violation of the abstinence goal) (18) and relapse (return to previous level of use, abandonment of abstinence goal) (18) to substance use following a quit attempt, as well as greater frequency of substance use post-quit (19,20). The present study aimed to examine the connection between PTSD and lapse (i.e. cannabis use), relapse (i.e. use on 4 of 7 consecutive days) (21,22), and frequency of use following a self-guided quit attempt among dependent cannabis users. We focused on individuals attempting a self-guided cessation attempt because the majority of cannabis-dependent individuals try to quit on their own rather than seek professional assistance (23). Military Veterans were chosen as the focus of the study as they have some of the highest rates of PTSD, as well as increasing rates of cannabis use disorders (1,24–26). Finally, we chose a 6-month window to observe the hypothesized effects as prior work indicates that this window is ample to observe the majority of lapses and relapses that occur postcannabis-cessation (22,27). We had two hypotheses: (i) we expected that, following a self-guided quit attempt, cannabisdependent individuals with PTSD would lapse and relapse to cannabis more quickly than their non-PTSD counterparts, and (ii) we expected that PTSD would change the trajectory of cannabis use following a self-guided quit attempt, such that individuals with PTSD would use cannabis more frequently and take longer to reduce their overall use than their non-PTSD counterparts.
PTSD Scale (28), 26 participants met DSM-IV (29) criteria for PTSD, while 78 participants did not. The majority of participants who did not meet criteria for PTSD were not exposed to trauma (50/78; 64.1%). Participants with and without co-occurring PTSD did not significantly differ in terms of age, gender, or education status (p’s40.16), but did differ in terms of race/ethnicity (2 (5) ¼ 16.17, p ¼ 0.006). Individuals with PTSD were more likely to be Hispanic (36.0% vs. 6.5%), while individuals without PTSD were more likely to be White/Caucasian (39.0% vs. 28.0%) or Black/ Non-Hispanic (41.6% vs. 20.0%). The majority of the participants (94.2%) had a current diagnosis of abuse or dependence of a substance other than cannabis (i.e. alcohol, opiates, sedative/hypnotics, cocaine, amphetamines, hallucinogens, inhalants). Additionally, 35.6% met criteria for a current anxiety disorder other than PTSD (i.e. panic disorder, generalized anxiety disorder, obsessive compulsive disorder, phobia [specific, agoraphobia, social]), and 42.3% met criteria for a current mood disorder (i.e. major depressive disorder, bipolar I/II disorder, dysthymia). Participants with co-occurring PTSD were significantly more likely to have an additional mood (2 (1) ¼ 11.77, p ¼ 0.001) or anxiety (2 (1) ¼ 8.92, p ¼ 0.003) disorder than participants without PTSD, but participants with and without PTSD were equally likely to have an additional substance-use disorder (2 (1) ¼ 2.23, p ¼ 0.14).
Methods
Psychiatric diagnoses
Participants
Prevalence of current Axis-I diagnoses, including cannabis dependence1 but excluding PTSD, was determined by the Structured Clinical Interview-Non-Patient Version for DSMIV (SCID-I-N/P) (30). The Clinician-Administered PTSD Scale (CAPS) (28) was used to assess the intensity and frequency of DSM-IV PTSD symptoms, and thus identify individuals meeting criteria for PTSD. Consistent with wellestablished diagnostic guidelines (31), participants were scored positive for a symptom when the intensity score was greater than or equal to one and the frequency score was greater than or equal to 2. Individuals were designated as meeting criteria for PTSD when they: (a) met DSM-IV diagnostic criteria A, (b) met diagnostic criteria for each of the three symptom clusters, and (c) obtained a CAPS severity score (i.e. frequency + intensity) of 45 or higher (32). The SCID-I-N/P and CAPS were administered by trained research assistants and all interviews were audio-recorded and diagnoses were confirmed by the first author following a review of recorded interviews.
Inclusion criteria were (i) being a US military Veteran, (ii) meeting diagnostic criteria for current cannabis dependence*, (iii) reporting a current level of motivation to quit of at least 5 on a 10 point scale (0 ¼ ‘‘no interest in quitting’’ to 10 ¼ ‘‘definite interest in quitting’’), and (iv) being interested in making a serious self-guided quit attempt. Exclusion criteria included (a) limited mental competency and inability to give informed, voluntary, written consent, (b) a significant change (decrease of425%) in amount of cannabis smoked per day during the previous month, (c) pregnancy or current breastfeeding, and (d) current suicidal ideation. A total of 107 participants met eligibility criteria. Three participants did not complete any of the listed measures and were thus excluded from analyses. Thus, participants were 104 cannabis-dependent military Veterans (95.2% male; Mage ¼ 50.90 years, SDage ¼ 9.90). These individuals reported their race/ethnicity as White/Caucasian (36.3%) or Black//Non-Hispanic (36.3%), Hispanic (13.7%), ‘‘Other’’ (11.8%), Black/Hispanic (1.0%), or Asian (1.0%). The majority of participants completed high school (93.2%), and 36.9% of participants graduated from a 2or 4-year college. Participants with co-occurring PTSD were actively recruited. As identified using the Clinician-Administered
*Diagnostic criteria for cannabis dependence were consistent with the definition set forth in the DSM-IV-TR (29), with the addition of withdrawal, consistent with DSM-5 (49).
Measures
Substance use and lapse/relapse The timeline follow-back (TLFB) procedure (33) was used to assess self-reported use of cannabis, as well as alcohol and tobacco. The TLFB was administered at baseline to determine mean cannabis, alcohol, and tobacco used on each day for the prior 90 days, and at each time-point post-quit to obtain substance use information following the cessation attempt. Quantity of cannabis used on each day was indexed by a graphical depiction that ranged from 0–8 (34).
Impact of PTSD on cannabis
DOI: 10.3109/00952990.2015.1043209
Downloaded by [University of Exeter] at 03:27 03 August 2015
Procedure Interested persons, responding to flyers posted throughout a VA Medical Center, contacted the research team and were provided with a description of the study via phone. Participants were initially screened for eligibility, and those eligible scheduled for a baseline appointment. Participants were instructed to schedule their appointment 1-day prior to the day that they would be willing to make a serious cannabis quit attempt. Upon arrival to the laboratory, each participant provided written consent to participate in the study. Next, participants were administered the SCID I-N/P (30) and CAPS (28) by trained interviewers to assess key exclusionary and inclusionary criteria. If deemed eligible, participants then completed the TLFB (33). At the conclusion of this appointment, participants were compensated $75 and instructed to make a serious quit attempt starting the morning of the following day. Participants returned to the lab at 1, 2, 3, and 4 weeks as well as 2, 3, 4, 5, and 6 months following the initiation of their quit attempt. At each follow-up, participants completed the TLFB and were compensated $15. All study procedures were approved by the VA and Stanford University Institutional Review Boards (IRBs). A Certificate of Confidentiality was also obtained from the National Institutes on Drug Abuse (NIDA) to protect participants in the reporting of their substance use behaviors.
Results The number of participants who provided data at each timepoint was: 94 (90.4% of total sample) at Week 1, 85 (81.7%) at Week 2, 83 (79.8%) at Week 3, 80 (76.9%) at Week 4, 78 (75.0%) at Month 2, 75 (72.1%) at Month 3, 74 (71.2%) at Month 4, 67 (64.4%) at Month 5 and 65 (62.5%) at Month 6. The percentage of participants providing data significantly differed at each time-point depending on PTSD diagnosis (2 (1, n ¼ 104) ¼ 6.20–14.05, ps50.05), with 18–37% more participants without a PTSD diagnoses providing data. We note that variation in sample size by analysis is due to different patterns of missing TLFB data. Descriptive statistics for mean cannabis, alcohol, and tobacco use at all time-points are shown in Table 1. Demonstrating the commitment of participants to quit using cannabis, repeated measures ANOVA analyses revealed that the mean use of cannabis was significantly reduced from baseline to each follow-up (all p50.001, all p2 4 0:59). Nevertheless, a majority of
individuals lapsed (n ¼ 72 out of 78 with data [92.3%]; defined as one or more use of cannabis), and relapsed (n ¼ 57 out of 77 with data [74.0%]; defined as use on 4 of 7 consecutive days), to cannabis use by the end of the cessation period. Primary analyses With a Cox regression, we used PTSD diagnosis to predict time to first lapse and relapse. PTSD diagnosis did not significantly predict time to first lapse (2 (1, n ¼ 75) ¼ 3.67, p ¼ 0.06; b ¼ 0.57, SE ¼ 0.30, p ¼ 0.06; exp[b] ¼ 0.57, CI [95%] ¼ 0.31–1.02). PTSD diagnosis also did not significantly predict time to first relapse (2 (1, n ¼ 74) ¼ 0.93, p ¼ 0.34; b ¼ 0.31, SE ¼ 0.32, p ¼ 0.34; exp[b] ¼ 0.74, CI [95%] ¼ 0.39–1.34). Using generalized linear mixed modeling (GLMM; as implemented by R) (35) we examined the association of PTSD diagnosis and the trajectory of mean cannabis use across the 6 months following the quit attempt (aggregated to nine time-points representing mean use during Weeks 1 through 4 and Months 2 through 6). Between-person parameters were estimated for: (a) the mean cannabis use score at the intercept for participants without PTSD, (b) the association between PTSD diagnosis and mean cannabis use scores at the intercept, (c) the average slope over time, and (d) the association between PTSD diagnosis and cannabis use trajectories. These latter parameters are measures of change per unit time associated with PTSD after accounting for baseline scores and the non-independence of observations. We hypothesized that a quadratic model best accounted for the data, given that cannabis use was likely to substantially decrease following the quit attempt, and then decrease more slowly or level off. Indeed, plotted data representing mean cannabis use for participants with and without PTSD over the cessation period (see Figure 1) supported this hypothesis, as did the better fit statistics of a GLMM including a quadratic slope and linear slope relative to a GLMM including a linear slope only. In our analysis, the intercept was allowed to vary between participants, and the restricted maximum likelihood estimation method and an unstructured covariance specification were used. In terms of the GLMM analysis, cannabis use was observed to significantly decrease in a linear (b ¼ 0.03, SE ¼ 0.04, Z ¼ 7.15, p50.001) and quadratic (b ¼ 0.01,
Table 1. Descriptive statistics. Cannabis use Mean (SD) Baseline Week 1 Week 2 Week 3 Week 4 Month 2 Month 3 Month 4 Month 5 Month 6
5.74 1.88 1.72 1.65 1.60 1.64 1.79 1.56 1.64 1.60
(2.07) (2.22)*** (2.26)*** (2.06)*** (2.06)*** (2.21)*** (2.42)*** (2.39)*** (2.30)*** (2.25)***
Alcohol use Range
1.50–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00 0.00–8.00
Mean (SD) 2.39 0.64 0.54 0.69 0.62 0.60 0.72 0.66 0.84 0.90
341
(4.98) (2.32)** (1.57)** (2.00)** (1.79)** (1.91)** (1.90)** (1.72)** (2.14)** (2.61)**
Tobacco use Range
0.00–32.52 0.00–20.00 0.00–10.00 0.00–10.86 0.00–10.71 0.00–12.00 0.00–11.00 0.00–9.00 0.00–10.00 0.00–13.46
*p50.05, **p50.01, ***p50.001 for comparisons with baseline value.
Mean (SD) 6.29 4.76 4.67 4.10 4.11 4.45 4.81 4.10 4.03 4.44
(8.01) (6.01)* (6.14) (5.86)* (5.30)* (6.10) (6.60) (6.26)* (6.50)* (6.84)*
Range 0.00–30.22 0.00–20.00 0.00–20.00 0.00–25.00 0.00–17.50 0.00–20.00 0.00–20.00 0.00–20.00 0.00–20.00 0.00–21.00
Mean Cannabis Use
342
M. O. Bonn-Miller et al. 8.00 7.00 6.00 5.00 4.00 3.00 2.00 1.00 .00
Am J Drug Alcohol Abuse, 2015; 41(4): 339–344
No PTSD Diagnosis PTSD Diagnosis
Downloaded by [University of Exeter] at 03:27 03 August 2015
Figure 1. Trajectories of mean cannabis use separately for participants with and without a posttraumatic stress disorder (PTSD) diagnosis.
SE ¼ 0.002, Z ¼ 5.97, p50.001) manner. We estimated mean cannabis use at the intercept among individuals without PTSD at 3.13 (SE ¼ 0.22, Z ¼ 14.23, p50.001). PTSD diagnosis significantly predicted greater mean cannabis use at baseline (b ¼ 1.35, SE ¼ 0.46, Z ¼ 2.95, p ¼ 0.003) and, during the cessation period, PTSD diagnosis significantly predicted the linear trajectory of cannabis use (b ¼ 0.21, SE ¼ 0.09, Z ¼ 2.37, p ¼ 0.02), and the quadratic trajectory of cannabis use at trend levels (b ¼ 0.007, SE ¼ 0.004, Z ¼ 1.71, p ¼ 0.09). In other words, PTSD diagnosis predicted the linear decrease in cannabis use over time, but did not significantly predict the instantaneous decrease in cannabis use after the cessation attempt (i.e. both groups with and without PTSD experienced this instantaneous decrease) (36). This can be seen in Figure 1, in which participants with and without PTSD experience steep initial declines in cannabis use. Participants with PTSD then continue to decline in cannabis use, whereas participants without PTSD tend to remain level in their cannabis use. Subsidiary analyses We conducted two post-hoc analyses to investigate whether observed findings remained after adjusting for (i) average alcohol and tobacco use during the cessation period, and (ii) co-occurring mood and anxiety disorder (other than PTSD) diagnoses. We interpreted results of the latter analysis with caution as individuals with and without PTSD meaningfully vary in terms of co-occurring diagnoses, with no valid statistical method to ‘‘control’’ for this difference (37). Adjusting for average alcohol and tobacco use during the cessation period, PTSD diagnosis continued to significantly predict greater mean cannabis use at baseline (b ¼ 1.31, SE ¼ 0.44, Z ¼ 2.99, p ¼ 0.003), as well as the linear trajectory of cannabis use by PTSD diagnosis (b ¼ 0.21, SE ¼ 0.09, Z ¼ 2.28, p ¼ 0.02), but not the quadratic trajectory of cannabis use (b ¼ 0.007, SE ¼ 0.004, Z ¼ 1.67, p ¼ 0.10). After adjusting for current mood and anxiety disorder diagnoses (other than PTSD), PTSD diagnosis continued to significantly predict greater mean cannabis use at baseline (b ¼ 1.40, SE ¼ 0.49, Z ¼ 2.86, p ¼ 0.004), as well as the linear trajectory of cannabis use by PTSD diagnosis (b ¼ 0.20, SE ¼ 0.10, Z ¼ 2.06, p ¼ 0.04), but not the quadratic trajectory of cannabis use (b ¼ 0.005, SE ¼ 0.003, Z ¼ 1.64, p ¼ 0.10). Thus, results remained similar in size and statistical significance when adjusting for covariates.
Discussion The present study is the first empirical investigation of the association between PTSD and cannabis cessation. Contrary to expectation and prior findings among substance users more broadly (15–17), a diagnosis of PTSD did not increase the risk of either a lapse or relapse to cannabis use following a selfguided cessation attempt. However, partially consistent with expectation and prior work (13), individuals with PTSD were more likely to (i) initially use cannabis at higher rates, and (ii) take longer to reduce their cannabis use at the beginning of the cessation period, than those without PTSD. Though our results also demonstrated a linear decline in cannabis use over the cessation period among those with PTSD, relative to consistent use among individuals without PTSD, it is important to contextualize these differences within the observed disparity in use directly following the quit attempt (see Figure 1). Indeed, as initial reductions in cannabis use were far smaller among participants with PTSD, there was greater room for reductions in use relative to the non-PTSD group later in the cessation period; there were little to no differences observed between groups after the first month of the cessation period. Importantly, post-hoc analyses revealed that the observed differences were between individuals with and without PTSD, and were not a function of alcohol or tobacco use, or co-occurring anxiety and mood disorders, which have independently been associated with cannabis dependence and quit success in prior investigations (38–40). Results from this investigation are consistent with a harmreduction perspective (41) as they show that observed differences were not in relation to abstinence, but rather reductions in use. Indeed, findings highlight the importance of examining multiple indices of substance use, rather than simply lapse and relapse, following a cessation attempt. Results also indicate that the categorical examination of PTSD provides important information in terms of understanding those at risk for poor initial cessation outcomes. The findings have some clinical implications. They suggest that individuals with PTSD have more difficulty initially reducing their cannabis use than individuals without PTSD, though differences between groups may disappear over time. In conjunction with prior empirical work, findings are consistent with a model whereby individuals with PTSD find cannabis to be a useful short-term coping strategy to reduce acute symptoms (e.g. poor sleep) (42). However, coping-oriented use among this population may lead to dependence and exacerbated symptoms of withdrawal and craving during cessation attempts (13,34). As cannabis withdrawal symptoms overlap with PTSD symptoms (43), individuals with PTSD may experience withdrawal as particularly aversive (44) and thus be more apt to continue to use cannabis at higher rates than their non-PTSD counterparts, particularly early during a cessation attempt when withdrawal would likely be most severe for this population (45). This is supported by data from the present study documenting that individuals with PTSD used cannabis at higher rates during the time at which cannabis withdrawal would have been at its worst (i.e. during the first 3 weeks of the quit attempt) (45). Though this model needs further empirical investigation, it appears likely that
Impact of PTSD on cannabis
Downloaded by [University of Exeter] at 03:27 03 August 2015
DOI: 10.3109/00952990.2015.1043209
cannabis-dependent individuals with PTSD may particularly benefit from withdrawal symptom management (e.g. dronabinol, zolpidem) (46,47) as well as specialized treatments that address the functional nature of cannabis use in terms of acute PTSD symptom alleviation. Although the findings are of interest, the present study is not without limitation. First, all assessments were obtained via self-report, and information regarding co-occurring psychosocial treatment receipt and prescription medication use were not collected. Though the self-report limitation is tempered by the use of well-validated ‘‘gold-standard’’ measures, some of which have been shown to be as effective as objective tests (e.g. TLFB) (48), future work would benefit from collecting data on concurrent psychosocial and pharmacological treatment receipt, employing multi-method assessments, particularly for PTSD symptoms, as well as testing of biological specimens (e.g. urine) to confirm self-report cannabis use status. Indeed, though cannabis use/abstinence was not confirmed via testing of biological specimens, as (i) there was no differential reinforcement for abstinence, and (ii) participants were informed that the study investigators received a Certificate of Confidentiality from NIDA, we have confidence in the validity of self-reported cannabis use during the study period. Second, the present study employed DSM-IV (29) criteria for cannabis dependence and PTSD diagnosis due to the timing of the study relative to DSM version. Though the diagnosis of cannabis dependence included withdrawal, as it was known by study investigators at the time of the investigation that this would be added as criteria for diagnosis in DSM-5 (49), given extensive revision to diagnostic criteria for both PTSD and cannabis dependence, future investigations would benefit from employing DSM-5 (49) criteria for PTSD and cannabis use disorder. Third, as the sample was comprised of military Veterans, the majority of whom were male, the generalizability of the findings are somewhat limited. However, the association between cannabis and PTSD has also been observed in epidemiological studies of non-Veteran populations (10), lending support for the applicability of these findings to more general, non-Veteran, populations. That said, future work would benefit from determining whether PTSD diagnosis is related to heightened cannabis use post-cessation attempt among female and non-military samples. Finally, though the present study purposefully recruited individuals who were interested in making a self-guided quit attempt, it is possible that the particularly high rates of lapse and relapse observed among this group may have hindered the ability to detect the effect of PTSD on time to lapse and relapse. Future work would benefit from replicating and extending the current investigation among individuals engaged in formal empirically-supported treatments for cannabis dependence (e.g. contingency management, cognitive-behavioral therapy) (50).
Funding This work was supported by a VA Clinical Science Research and Development (CSR&D) Career Development Award – 2, granted to Dr. Bonn-Miller. The expressed views do not necessarily represent those of the Department of Veterans Affairs.
343
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.
References 1. Bonn-Miller MO, Harris AH, Trafton JA. Prevalence of cannabis use disorder diagnoses among veterans in 2002, 2008, and 2009. Psycholog Services 2012;9:404–416. 2. Substance Abuse and Mental Health Services Administration (SAMHSA). Results from the 2012 National Survey on Drug Use and Health: summary of National Findings. Rockville (MD): SAMHSA; 2013. 3. Institute of Medicine. Treatment for posttraumatic stress disorder in military and veteran populations: final assessment. Washington, DC: Institute of Medicine; 2014. 4. Bremner JD, Southwick SM, Darnell A, Charney DS. Chronic PTSD in Vietnam combat veterans: course of illness and substance abuse. Am J Psychiatry 1996;153:369–375. 5. Kilpatrick DG, Acierno R, Saunders B, Resnick HS, Best CL, Schnurr PP. Risk factors for adolescent substance abuse and dependence: data from a national sample. J Consul Clin Psychol 2000;68:19–30. 6. Vlahov D, Galea S, Resnick H, Ahern J, Boscarino JA, Bucuvalas M, Gold J, et al. Increased use of cigarettes, alcohol, and marijuana among Manhattan, New York, residents after the September 11th terrorist attacks. Am J Epidemiol 2002;155:988–996. 7. Program Evaluation and Resource Center VA; 2014. 8. Bonn-Miller MO, Boden MT, Bucossi MM, Babson KA. Selfreported cannabis use characteristics, patterns and helpfulness among medical cannabis users. Am J Drug Alcohol Abuse 2014;40: 23–30. 9. Bohnert KM, Perron BE, Ashrafioun L, Kleinberg F, Jannausch M, Ilgen MA. Positive posttraumatic stress disorder screens among first-time medical cannabis patients: prevalence and association with other substance use. Addict Behav 2014;39:1414–1417. 10. Cougle JR, Bonn-Miller MO, Vujanovic AA, Zvolensky MJ, Hawkins KA. Posttraumatic stress disorder and cannabis use in a nationally representative sample. Psychol Addictive Behav 2011; 25:554–558. 11. Bonn-Miller MO, Vujanovic AA, Drescher KD. Cannabis use among military veterans after residential treatment for posttraumatic stress disorder. Psychol Addictive Behav 2011;25:485–491. 12. Bonn-Miller MO, Vujanovic AA, Feldner MT, Bernstein A, Zvolensky MJ. Posttraumatic stress symptom severity predicts marijuana use coping motives among traumatic event-exposed marijuana users. J Traumatic Stress 2007;20:577–586. 13. Boden MT, Babson KA, Vujanovic AA, Short NA, Bonn-Miller MO. Posttraumatic stress disorder and cannabis use characteristics among military veterans with cannabis dependence. Am J Addictions/Am Acad Psychiat Alcohol Addict 2013;22:277–284. 14. Bonn-Miller MO, Boden MT, Vujanovic AA, Drescher KD. A prospective investigation of the impact of cannabis use disorders on posttraumatic stress disorder symptoms among veterans in residential treatment. Psycholog Trauma: Theory Res Pract Policy 2013;5:193–200. 15. Ouimette PC, Ahrens C, Moos RH, Finney JW. Posttraumatic stress disorder in substance abuse patients: relationship to 1-year posttreatment outcomes. Psychol Addict Behav 1997;11:34–47. 16. Ouimette PC, Finney JW, Moos RH. Two-year posttreatment functioning and coping of substance abuse patients with posttraumatic stress disorder. Psychol Addict Behav 1999;13:105–114. 17. Read JP, Brown PJ, Kahler CW. Substance use and posttraumatic stress disorders: symptom interplay and effects on outcome. Addict Behav 2004;29:1665–1672. 18. Larimer ME, Palmer RS, Marlatt GA. Relapse prevention. An overview of Marlatt’s cognitive-behavioral model. Alcohol Res Health 1999;23:151–160. 19. Ouimette P, Brown PJ. Trauma and substance abuse: causes, consequences, and treatment of comorbid disorders, 1st ed. Washington, DC: American Psychological Association; 2003. 20. Ouimette PC, Brown PJ, Najavits LM. Course and treatment of patients with both substance use and posttraumatic stress disorders. Addict Behav 1998;23:785–795.
Downloaded by [University of Exeter] at 03:27 03 August 2015
344
M. O. Bonn-Miller et al.
21. Hall SM, Havassy BE, Wasserman DA. Commitment to abstinence and acute stress in relapse to alcohol, opiates, and nicotine. J Consult Clin Psychol 1990;58:175–181. 22. Moore BA, Budney AJ. Relapse in outpatient treatment for marijuana dependence. J Substance Abuse Treat 2003;25:85–89. 23. Cunningham JA. Remissions from drug dependence: is treatment a prerequisite? Drug Alcohol Depend 2000;59:211–213. 24. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62:593–602. 25. Seal KH, Metzler TJ, Gima KS, Bertenthal D, Maguen S, Marmar CR. Trends and risk factors for mental health diagnoses among Iraq and Afghanistan veterans using Department of Veterans Affairs health care, 2002–2008. Am J Public Health 2009;99:1651–1658. 26. Weiss DS, Marmar CR, Schlenger WE, Fairbank JA, Jordan BK, Hough RL, Kulka RA. The prevalence of lifetime and partial posttraumatic stress disorder in Vietnam theater veterans. J Traumatic Stress 1992;5:365–376. 27. McRae AL, Budney AJ, Brady KT. Treatment of marijuana dependence: a review of the literature. J Substance Abuse Treat 2003;24:369–376. 28. Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM. The development of a ClinicianAdministered PTSD Scale. J Traumatic Stress 1995;8:75–90. 29. American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders: DSM-IV-TR, 4th ed. Washington, DC: APA; 2000. 30. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV-TR Axis I disorders, Research Version, Non-patient edition. New York: Biometrics Research, New York State Psychiatric Institute; 2002. 31. Weathers FW, Keane TM, Davidson JR. Clinician-administered PTSD scale: a review of the first ten years of research. Depression Anxiety 2001;13:132–156. 32. Weathers FW, Ruscio AM, Keane TM. Psychometric properties of nine scoring rules for the Clinician-Administered Posttraumatic Stress Disorder Scale. Psychological Assess 1999;11:124–133. 33. Sobell L, Sobell M. Timeline follow-back: a technique for assessing self-reported ethanol consumption. In: Allen J, Litten RZ, eds. Measuring alcohol consumption: psychosocial and biological methods; Totowa (NJ): Humana Press; 1992:41–72. 34. Bonn-Miller MO, Zvolensky MJ. An evaluation of the nature of marijuana use and its motives among young adult active users. Am J Addictions/Am Acad Psychiatrists Alcohol Addict 2009;18: 409–416. 35. Ihaka R, Gentleman R. R: a language for data analysis and graphics. J Computat Graphical Stat 1996;5:299–314.
Am J Drug Alcohol Abuse, 2015; 41(4): 339–344
36. Singer JD, Willett JB. Applied longitudinal data analysis: modeling change and event occurrence. Oxford/New York: Oxford University Press; 2003. 37. Miller GA, Chapman JP. Misunderstanding analysis of covariance. J Abnormal Psychol 2001;110:40–48. 38. Rooke SE, Norberg MM, Copeland J. Successful and unsuccessful cannabis quitters: comparing group characteristics and quitting strategies. Subst Abuse Treat, Prevent Policy 2011;6:30. 39. Degenhardt L, Hall W. The relationship between tobacco use, substance-use disorders and mental health: results from the National Survey of Mental Health and Well-being. Nicotine Tobacco Res 2001;3:225–234. 40. Buckner JD, Schmidt NB, Lang AR, Small JW, Schlauch RC, Lewinsohn PM. Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence. J Psychiatric Res 2008; 42:230–239. 41. Marlatt GA. Harm reduction: come as you are. Addict Behav 1996; 21:779–788. 42. Babson KA, Bonn-Miller MO. Sleep disturbances: implications for cannabis use, cannabis use cessation, and cannabis use treatment. Curr Addict Rep 2014;1:109–114. 43. Budney AJ, Hughes JR, Moore BA, Vandrey R. Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry 2004;161:1967–1977. 44. Bonn-Miller MO, Zvolensky MJ, Marshall EC, Bernstein A. Incremental validity of anxiety sensitivity in relation to marijuana withdrawal symptoms. Addict Behav 2007;32:1843–1851. 45. Budney AJ, Moore BA, Vandrey RG, Hughes JR. The time course and significance of cannabis withdrawal. J Abnormal Psychol 2003; 112:393–402. 46. Vandrey R, Smith MT, McCann UD, Budney AJ, Curran EM. Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal. Drug Alcohol Depend 2011;117:38–44. 47. Vandrey R, Stitzer ML, Mintzer MZ, Huestis MA, Murray JA, Lee D. The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users. Drug Alcohol Depend 2013;128: 64–70. 48. Hjorthoj CR, Hjorthoj AR, Nordentoft M. Validity of timeline follow-back for self-reported use of cannabis and other illicit substances – systematic review and meta-analysis. Addict Behav 2012;37:225–233. 49. American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders: DSM-5, 5th ed. Washington, DC: APA; 2013. 50. Roffman RA, Stephens RS. Cannabis dependence: its nature, consequences, and treatment. Cambridge, UK/New York: Cambridge University Press; 2006.
