The youth were monitored with supervised urine and breath samples every 3-4 days for 28 days. If all toxicology tests were negative, the youth was scheduled for psychological evaluation and imaging. These sessions included a brief questionnaire and interview , neuropsychological evaluation, hair sample toxicology to confirm the urine toxicology results, and magnetic resonance imaging . Of eligible MJ-using youth who initiated monitored abstinence, 29% had data suggesting substance use during the 28-day period. Youth who did not maintain abstinence were discontinued and compensated for their time. Upon completion of the study, youth and parents/guardians received financial compensation. Removal of non-brain materials from each T1-weighted 3D anatomical dataset used a combination of a hybrid watershed and deformable surface semi-automated skull-stripping program and manual editing. All manual editing was performed in AFNI by trained assistants blind to participant characteristics who attained high levels of inter- and intra-rater reliability prior to data collection. Next, fully skull-stripped T1 anatomical images were processed using the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain’s automated segmentation tool . Utilizing a hidden Markov random field model and an associated expectation-maximization algorithm,vertical farming this automated program was used to segment the white matter of the brain from other tissue types . Hippocampal regions of interest were manually traced on contiguous 1.3 mm slices in the coronal plane through the structure by trained assistants blind to participant characteristics .
Briefly, the stereotactic boundaries were as follows: anterior: coronal slice through the fullest portion of the mammillary bodies; superior/lateral: temporal horn and alveus; inferior: white matter of the parahippocampal gyrus; medial: ambient cistern; posterior: columns of the fornix. All volumes were analyzed as a ratio to overall intracranial volume to control for individual variability in brain size . The primary analysis included three series of multiple regressions that tested whether white matter or hippocampal volume was significantly associated with depressive symptoms after controlling for marijuana use group status, gender, alcohol use, and interactions between group and white matter/hippocampal volume. Specifically, three regressions testing the relationship between each independent variable of interest [overall white matter volume/ICV, left hippocampal volume/ICV, or right hippocampal volume/ICV] and each dependent variable were run, totaling six regressions.Independent variables were entered first as a block : white matter or hippocampal volume, group, lifetime alcohol use, and gender. Interactions between brain volume and group were then entered as a second block.As stated earlier, a series of regressions was run to predict depressive symptoms on the BDI and HAM-D. Predictor: White Matter Volume. When predicting BDI scores, there was a significant interaction between group membership and white matter volume indicated that, among MJ-users only, smaller white matter volume was associated with higher depressive scores. For the HAM-D, smaller white matter volume was significantly associated with higher levels of depressive symptoms among all the adolescents .
MJ-users , and all female adolescents reported higher scores on the HAM-D. Predictor: Hippocampal Volume. No hippocampal variables predicted depressive symptoms on the BDI or HAM-D. When hippocampal volumes were predictors instead of white matter volume, similar relationships were found between group status and gender and HAM-D scores in that MJ-users and female adolescents reported higher scores. The primary findings revealed that marijuana use and white matter volume were additive and interactive in predicting depressive symptoms among adolescents. It is notable that the relationship between white matter volume and depressive symptoms was observed in a sample of adolescents who did not meet past or current criteria for a depressive disorder. Therefore, the findings are not confounded by the influences of mood disorder duration or psychiatric medications. Consistent with previous research, we also found that marijuana users had significantly higher scores on a depression rating scale compared to the controls. The relationship between reduced white matter volume and increased depressive symptoms in this sample may be driven primarily by disruption in the frontal-limbic-basal ganglia circuitry . Indeed, differences in prefrontal white matter volume and integrity have been shown in pediatric , adolescent , adult, and elderly depressed patients compared to non-depressed controls. Among depressed adolescents, it has been hypothesized that reduced prefrontal lobe white matter volume is due to abnormal myelination during neuromaturation . However, it remains difficult to determine whether abnormal neurodevelopment caused depression, or if depression interrupts developmental myelination. Notably, we found that the relationship between smaller white matter volume and increased depressive symptoms was most prominent among the marijuana users. Due to the cross-sectional nature of this study, the directional and temporal relationship of white matter volume, marijuana use, and depressive symptoms cannot be ascertained. One possible explanation for these findings is that the MJ users demonstrated increased variance in depressive symptoms compared to controls, especially on the BDI; therefore, statistical relationships were more likely to be observed in this group compared to controls. However, we did detect a small difference in the correlations between the HAM-D and white matter volume between the groups.
Therefore, based on these findings and previous research demonstrating higher rates of depressive symptoms among marijuana users , webelieve that the current results support the hypothesis that chronic marijuana use may cause or worsen depressive symptoms. In turn, morphological abnormalities may be observed earlier in the mood disorder process among marijuana users. The endogenous cannabinoid receptors are found in brain regions associated with mood regulation, such as limbic and frontal areas, as well as white matter . Therefore, it is possible that chronic marijuana use may alter white matter tracts in these areas , directly causing depressive symptoms. However, we did not find white matter volume differences between the groups, although differences in white matter microstructure may exist. Still, we believe it is unlikely that marijuana use is directly or solely responsible for the subtle white matter abnormalities associated with depressive symptoms in this sample. A possible alternative is that chronic marijuana use worsens existing depressive symptoms by disrupting the neuronal functioning of the frontal and limbic brain circuits . Due to compromised neuronal functioning in these areas, adolescent marijuana users may be less able to compensate for additional neuropathological processes associated with depressive symptoms. Finally, this observed interaction between marijuana use and white matter could be due to other moderating factors,flood tray such as shared genetic or environmental vulnerability for both disorders . We did not find relationships between hippocampal volume and depressive symptoms in this sample of adolescents. It is possible that hippocampal volume reductions occur later in the depressive disorder course . However, the current findings are consistent with studies focused on depressed pediatric patients and medication free young adults . Therefore, the relationship between hippocampal volume and depressive symptoms may occur primarily in the elderly , particularly those with comorbid cerebrovascular disease . Some limitations of this study warrant consideration.
Although comparable to previous neuroimaging studies, the sample size is relatively small, which may influence generalizability and power. Further, the control group had limited variability of depressive symptoms, which may have influenced the group-white matter interaction results. Samples with substantially different patterns of substance use may yield different results. Further, the marijuana users had greater histories of alcohol and other drug use, although these variables were not related to depressive symptoms or white matter in this sample. Still, statistical control is not equivalent to matching, so it is possible that the combination of alcohol and marijuana use contributed to these findings. In summary, the present study found significant negative relationships between white matter volume and depressive symptoms in adolescents, especially among marijuana users. These structural findings may be primarily due to frontal-limbic-basal ganglia circuitry disruption. Therefore, further research investigating white matter integrity in specific regions of interest combining morphological analysis with diffusion tensor imaging in adolescent marijuana users is warranted. Further, longitudinal studies are needed to examine the developmental course of brain structure in conjunction with depressive symptoms among substance-using and non-using adolescents. People who use marijuana also tend to smoke cigarettes . Our systematic review of 163 studies published between 1999 and 2009 found that 85% of relationships studied indicated a significant, positive association between tobacco and marijuana use among youth and young adults . Few studies sought to intervene on tobacco and marijuana use, and findings were mixed. A better understanding of the interplay of tobacco and marijuana use is needed to aid intervention development. From a social cognitive perspective, understanding expectancies of the interaction between smoking and substance use may help identify perceived barriers to quitting and inform strategies for treatment engagement . For this purpose, Rohsenow et al. developed the Nicotine and Other Substance Interaction Expectancies Questionnaire to measure expectancies regarding the interaction between use of tobacco and other substance use. In the NOSIE development study of 160 patients from an inner-city residential substance abuse treatment program, Rohsenow et al. found that substance abuse consistently correlated with increased tobacco use and urges to smoke, while tobacco use increased substance use behavior and urges much less frequently. In a follow-up study with 162 veterans enrolled in a clinical trial for smoking cessation, Carmody et al. found similarly that participants expected smoking to have less of an impact on substance use than substance use has on smoking. In both studies, type of substance was not specified. The NOSIE has not been evaluated with respect to a specific substance such as marijuana nor among young adults. Given that tobacco and marijuana are both smoked substances and their use is common among young people , there is reason to believe that thoughts about the relationship between these two substances would be strong.
The primary objective of the present study was to adapt the NOSIE to pertain to tobacco and marijuana use and evaluate its use in a community sample of young adult smokers who also smoke marijuana. Specifically, we sought to confirm the 3-factor structure of the NAMIE based on three of the four original NOSIE scales with young adults and investigate relationships between tobacco-marijuana use interaction expectancies and 1) various indices of concurrently measured tobacco and marijuana use; 2) days co-using tobacco and marijuana; 3) thoughts about abstinence for tobacco and marijuana; and 4) tobacco and marijuana stages of change. Participants were English-literate young adult tobacco users age 18 to 25 recruited via an anonymous online survey. Those who reported use of cigarettes and marijuana in the past 30 days were included in the present analyses. Recruitment and data collection procedures have been described in detail previously . Of the 3748 cases that met criteria for survey completion , 1987 completed the survey. Of those, included for the current study were 1152 participants who indicated on two separate measures that they had used marijuana at least once in the past month. This study provides support for the validity of the Nicotine and Marijuana Interaction Expectancy questionnaire in a non-treatment seeking community sample of young adult tobacco and marijuana users. The three scales demonstrated utility in evaluating expectancies of the interaction of tobacco and marijuana for a non-treatment population. Expectations regarding the interaction of tobacco and marijuana use were lower in our sample than reported in other studies with the original NOSIE . Young adults in the community who use both tobacco and marijuana may be more receptive to an intervention targeting both substances than older adults who use tobacco and other drugs of abuse. This is consistent with findings with adolescents that treating tobacco dependence in the context of substance abuse treatment has promise for both tobacco and other drug outcomes . As hypothesized, young adults who used more tobacco and marijuana and used both substances in the same day generally held higher expectancies of interaction of these substances. Further, reports of smoking cigarettes to cope with marijuana urges to use were greater among young adults desiring and preparing to quit marijuana, yet possessing greater marijuana craving, perceiving lower expected success and greater difficulty in achieving marijuana abstinence. Having made a prior quit attempt did not affect expectations. Substituting tobacco for marijuana may be a common strategy to cope with marijuana urges among young adults who want to quit but do not have tools to do so, regardless of whether they have tried in the past.