The Interaction of Opiate Misuse and Marijuana Use on Behavioral Health Outcomes Using the Traumatic Brain Injury Model Systems Pain Collaborative Dataset.

OBJECTIVE: To determine if the interaction of opiate misuse and marijuana use frequency is associated with behavioral health outcomes. SETTING: Community. PARTICIPANTS: Three thousand seven hundred fifty participants enrolled in the Traumatic Brain Injury Model Systems who completed the Pain Survey and had complete opioid use and marijuana use information. DESIGN: Cross-sectional, secondary analysis from a multisite observational cohort. MAIN OUTCOME MEASURES: Clinically significant behavioral health symptoms for posttraumatic stress disorder (PTSD), depression, anxiety, and sleep quality. RESULTS: Three thousand five hundred thirty-five (94.3%) participants did not misuse opiates, 215 (5.7%) did misuse opiates (taking more opioid pain medication than prescribed and/or using nonprescription opioid pain medication); 2683 (70.5%) participants did not use marijuana, 353 (9.3%) occasionally used marijuana (less than once a week), and 714 (18.8%) regularly used marijuana (once a week or more frequently). There was a statistically significant relationship (P < .05) between the interaction of opiate misuse and marijuana use frequency and all behavioral health outcomes and several covariates (age, sex, cause of injury, severity of injury, and pain group category). Pairwise comparisons confirm that statistically significant associations on behavioral health outcomes are driven by endorsing opiate misuse and/or regular marijuana use, but occasional marijuana use was not associated. CONCLUSIONS: Higher odds of clinically significant PTSD, depression, anxiety, and poor sleep quality are present in people with traumatic brain injury (TBI) who misuse opiates and/or who use marijuana regularly. In the absence of opiate misuse, regular marijuana use had higher odds of worse behavioral health outcomes than occasional and no use. The interaction of opiate misuse and regular marijuana use yielded the highest odds. Individuals with TBI should be informed of the relationship of substance use and behavioral health outcomes and that current chronic pain may mediate the association.

Association Between Stimulant Treatment and Substance Use Through Adolescence Into Early Adulthood.

Importance: Possible associations between stimulant treatment of attention-deficit/hyperactivity disorder (ADHD) and subsequent substance use remain debated and clinically relevant. Objective: To assess the association of stimulant treatment of ADHD with subsequent substance use using the Multimodal Treatment Study of ADHD (MTA), which provides a unique opportunity to test this association while addressing methodologic complexities (principally, multiple dynamic confounding variables). Design, Setting, and Participants: MTA was a multisite study initiated at 6 sites in the US and 1 in Canada as a 14-month randomized clinical trial of medication and behavior therapy for ADHD but transitioned to a longitudinal observational study. Participants were recruited between 1994 and 1996. Multi-informant assessments included comprehensively assessed demographic, clinical (including substance use), and treatment (including stimulant treatment) variables. Children aged 7 to 9 years with rigorously diagnosed DSM-IV combined-type ADHD were repeatedly assessed until a mean age of 25 years. Analysis took place between April 2018 and February 2023. Exposure: Stimulant treatment of ADHD was measured prospectively from baseline for 16 years (10 assessments) initially using parent report followed by young adult report. Main Outcomes and Measures: Frequency of heavy drinking, marijuana use, daily cigarette smoking, and other substance use were confidentially self-reported with a standardized substance use questionnaire. Results: A total of 579 children (mean [SD] age at baseline, 8.5 [0.8] years; 465 [80%] male) were analyzed. Generalized multilevel linear models showed no evidence that current (B [SE] range, -0.62 [0.55] to 0.34 [0.47]) or prior stimulant treatment (B [SE] range, -0.06 [0.26] to 0.70 [0.37]) or their interaction (B [SE] range, -0.49 [0.70] to 0.86 [0.68]) were associated with substance use after adjusting for developmental trends in substance use and age. Marginal structural models adjusting for dynamic confounding by demographic, clinical, and familial factors revealed no evidence that more years of stimulant treatment (B [SE] range, -0.003 [0.01] to 0.04 [0.02]) or continuous, uninterrupted stimulant treatment (B [SE] range, -0.25 [0.33] to -0.03 [0.10]) were associated with adulthood substance use. Findings were the same for substance use disorder as outcome. Conclusions and Relevance: This study found no evidence that stimulant treatment was associated with increased or decreased risk for later frequent use of alcohol, marijuana, cigarette smoking, or other substances used for adolescents and young adults with childhood ADHD. These findings do not appear to result from other factors that might drive treatment over time and findings held even after considering opposing age-related trends in stimulant treatment and substance use.

Evidencia científica actualizada del tratamiento con cannabis medicinal en pacientes con dolor crónico / Current evidence of medical cannabis treatment in patients with chronic pain

El cannabis medicinal ha sido promovido por los medios de comunicación y por la opinión pública en general. La planta del cannabis y los medicamentos a base de cannabis (CbM) han pasado por alto los estudios tradicionales basados en la evidencia, y han sido legalizados en muchos países sin pasar por el camino habitual de aprobación de los medicamentos. La comunidad médica debe conocer la evidencia actual al respecto para poder asesorar de manera competente a los pacientes. Esta revisión explicará brevemente la situación actual de la evidencia, de los obstáculos encontrados y de los posicionamientos de las respectivas sociedades del dolor respecto a la utilización del cannabis medicinal para el tratamiento del dolor.(AU)

Medical cannabis has been promoted by the media and by public opinion. The cannabis herb and cannabis-based medicines have bypassed traditional evidence-based studies, and have been legalized in many countries without going through the usual path of drug approval. The medical community must be aware of the current evidence in this regard in order to appropriately advise patients. This review will explain the current status of the evidence, the obstacles encountered to obtain evidence, and the positions of the respective pain societies regarding the use of medicinal cannabis for the treatment of pain.(AU)

Association between marijuana use and nonmedical prescription opioid use in the United States: are we shifting from one epidemic to another?

The United States (US) is grappling with a severe opioid epidemic. Marijuana is emerging as a therapy for pain management and an alternative to opioids, but little evidence supports its long-term benefits. This study aims to examine the association of marijuana use among patients on prescription pain relievers in a retrospective cross-sectional study using zero-inflated negative binomial regression. The recipients of prescription pain medicines were identified using National Survey on Drug Use and Health (2015-2017). Irrespective of the state marijuana laws, marijuana use days were 34% higher and odds of having zero days of marijuana use were 73% lower in those using nonmedical prescription opioids vs. not (IRR = 1.34, p < 0.0001; OR = 0.27, p < 0.0001, respectively). In the absence of consequential evidence supporting marijuana for pain management and more states venturing into legalizing it, there needs to be more caution as the country struggles to recover from one epidemic.

Medical Marijuana Laws, Marijuana Use, and Opioid-Related Outcomes among Women in the United States.

BACKGROUND: In the context of the opioid epidemic, a limited but growing body of literature has found state medical marijuana laws (MMLs) to be associated with lower levels of opioid prescribing. However, robust evidence linking state MMLs with individual-level opioid-related outcomes is lacking, particularly among women. This finding is especially true for pregnant and parenting women, who have been disproportionately affected by the opioid crisis. METHODS: Using data drawn from the 2002-2014 National Survey on Drug Use and Heath, the study uses a difference-in-differences estimation strategy to compare opioid-related outcomes (opioid misuse initiation, opioid misuse in the past month and past year, and opioid use disorder) among all women, pregnant women, and parenting women in states with and without MMLs (before and after implementation). The study also investigates the impact of MMLs on marijuana use and marijuana use disorder. RESULTS: The findings indicate that MMLs were not associated with opioid misuse, opioid misuse initiation, or opioid use disorder among all women, pregnant women, and parenting women. These laws were, however, positively correlated with marijuana use and marijuana use disorder among all women and women with children. In addition, MMLs were associated with an increase in the frequency of opioid misuse for pregnant women and a decrease in the frequency of opioid misuse for parenting women. CONCLUSIONS: This finding suggests that, although medical marijuana may be viewed by some as a substitute for opioid analgesics, MMLs may not be an effective policy tool to tackle the opioid epidemic among women, especially pregnant and parenting women.

Stress and drug abuse-related disorders: The promising therapeutic value of neurosteroids focus on pregnenolone-progesterone-allopregnanolone pathway.

The pregnenolone-progesterone-allopregnanolone pathway is receiving increasing attention in research on the role of neurosteroids in pathophysiology, particularly in stress-related and drug use disorders. These disorders involve an allostatic change that may result from deficiencies in allostasis or adaptive responses, and may be downregulated by adjustments in neurotransmission by neurosteroids. The following is an overview of findings that assess how pregnenolone and/or allopregnanolone concentrations are altered in animal models of stress and after consumption of alcohol or cannabis-type drugs, as well as in patients with depression, anxiety, post-traumatic stress disorder or psychosis and/or in those diagnosed with alcohol or cannabis use disorders. Preclinical and clinical evidence shows that pregnenolone and allopregnanolone, operating according to a different or common pharmacological profile involving GABAergic and/or endocannabinoid system, may be relevant biomarkers of psychiatric disorders for therapeutic purposes. Hence, ongoing clinical trials implicate synthetic analogs of pregnenolone or allopregnanolone, and also modulators of neurosteroidogenesis.

In Vivo Imaging of Translocator Protein in Long-term Cannabis Users.

Importance: Cannabis is the most commonly used illicit drug in the world. Cannabinoids have been shown to modulate immune responses; however, the association of cannabis with neuroimmune function has never been investigated in vivo in the human brain. Objective: To investigate neuroimmune activation or 18-kDa translocator protein (TSPO) levels in long-term cannabis users, and to evaluate the association of brain TSPO levels with behavioral measures and inflammatory blood biomarkers. Design, Setting, and Participants: This cross-sectional study based in Toronto, Ontario, recruited individuals from January 1, 2015, to October 30, 2018. Participants included long-term cannabis users (n = 24) and non-cannabis-using controls (n = 27). Cannabis users were included if they had a positive urine drug screen for only cannabis and if they used cannabis at least 4 times per week for the past 12 months and/or met the criteria for cannabis use disorder. All participants underwent a positron emission tomography scan with [18F]FEPPA, or fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide. Main Outcomes and Measures: Total distribution volume was quantified across regions of interest. Stress and anxiety as well as peripheral measures of inflammatory cytokines and C-reactive protein levels were also measured. Results: In total, 24 long-term cannabis users (mean [SD] age, 23.1 [3.8] years; 15 men [63%]) and 27 non-cannabis-using controls (mean [SD] age, 23.6 [4.2] years; 18 women [67%]) were included and completed all study procedures. Compared with the controls, cannabis users had higher [18F]FEPPA total distribution volume (main group effect: F1,48 = 6.5 [P = .01]; ROI effect: F1,200 = 28.4 [P < .001]; Cohen d = 0.6; 23.3% higher), with a more prominent implication for the cannabis use disorder subgroup (n = 15; main group effect: F1,39 = 8.5 [P = .006]; ROI effect: F1,164 = 19.3 [P < .001]; Cohen d = 0.8; 31.5% higher). Greater TSPO levels in the brain were associated with stress and anxiety and with higher circulating C-reactive protein levels in cannabis users. Conclusions and Relevance: The results of this study suggest that TSPO levels in cannabis users, particularly in those with cannabis use disorder, are higher than those in non-cannabis-using controls. The findings emphasize the need for more complementary preclinical systems for a better understanding of the role of cannabinoids and TSPO in neuroimmune signaling.

Characteristics and Patterns of Marijuana Use in Community-Dwelling Older Adults.

OBJECTIVES: To understand patterns of marijuana use in community-dwelling older adults in Colorado. DESIGN: Anonymous survey. SETTING: Two academic geriatric primary care clinics. PARTICIPANTS: English-speaking individuals. MEASUREMENTS: We assessed self-reported characteristics and patterns of marijuana use and effect on targeted symptoms. Survey analysis focused on current users, defined as individuals who had used marijuana in the past 3 years. RESULTS: Three hundred forty-five individuals completed the survey (55% response rate); 113 (32%) had used marijuana in the past, of whom 55 (16%) had used since legalization. More than half of current users were aged 75 and older, and one-quarter were aged 85 and older. Most current users were white women. Of current users, 44% used marijuana products at least weekly for common conditions including chronic pain, depression, anxiety, and insomnia, and most found marijuana helpful for these conditions. Most respondents reported obtaining marijuana recreationally (67%) without a prescription. Nine respondents reported negative side effects attributable to marijuana use. CONCLUSION: To our knowledge, this is the first study to characterize marijuana use of older adults in a state in which it is legal for medical and recreational use. Marijuana was used for several common geriatric conditions, and respondents reported few side effects. The small number of survey respondents, the lack of generalizability in states where marijuana sales are illegal, and participation bias were the main study limitations. Further research is needed to better understand useful or harmful effects in this population. J Am Geriatr Soc 66:2167-2171, 2018.