Are prescription misuse and illicit drug use etiologically distinct? A genetically-informed analysis of opioids and stimulants.

BACKGROUND: Drug classes are grouped based on their chemical and pharmacological properties, but prescription and illicit drugs differ in other important ways. Potential differences in genetic and environmental influences on the (mis)use of prescription and illicit drugs that are subsumed under the same class should be examined. Opioid and stimulant classes contain prescription and illicit forms differentially associated with salient risk factors (common route of administration, legality), making them useful comparators for addressing this etiological issue. METHODS: A total of 2410 individual Australian twins [Mage = 31.77 (s.d. = 2.48); 67% women] were interviewed about prescription misuse and illicit use of opioids and stimulants. Univariate and bivariate biometric models partitioned variances and covariances into additive genetic, shared environmental, and unique environmental influences across drug types. RESULTS: Variation in the propensity to misuse prescription opioids was attributable to genes (41%) and unique environment (59%). Illicit opioid use was attributable to shared (71%) and unique (29%) environment. Prescription stimulant misuse was attributable to genes (79%) and unique environment (21%). Illicit stimulant use was attributable to genes (48%), shared environment (29%), and unique environment (23%). There was evidence for genetic influence common to both stimulant types, but limited evidence for genetic influence common to both opioid types. Bivariate correlations suggested that prescription opioid use may be more genetically similar to prescription stimulant use than to illicit opioid use. CONCLUSIONS: Prescription opioid misuse may share little genetic influence with illicit opioid use. Future research may consider avoiding unitary drug classifications, particularly when examining genetic influences.

Current attention-deficit/hyperactivity disorder and nonmedical prescription opioid use attributed to tramadol among male adolescents without conduct disorder in Egypt.

Background: Evidence for the association between attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) is common. However, little research has investigated this relationship among adolescents using nonmedical prescription opioids, particularly tramadol.Objective: To estimate the prevalence and correlates of ADHD among adolescents with tramadol misuse and without conduct disorder (CD).Methods: This study included 122 Egyptian adolescents (100% male) with opioid use disorders attributed to tramadol. The diagnosis of SUDs, ADHD, and CD (to exclude) was based on the SCID-I criteria of the DSM-IV-TR. Drug-related problems were assessed using the Drug Use Disorders Identification Test (DUDIT). All adolescents were screened for drugs by urinalysis.Results: Thirty-eight percent of adolescents with tramadol misuse had ADHD. Adolescents with tramadol misuse and ADHD were more likely to have a younger age of onset of smoking, substance use, and tramadol misuse than adolescents without ADHD.Conclusions: ADHD is common among adolescents with tramadol misuse. There is an association between ADHD and young age of onset of tramadol misuse and drug-related problems.

"Stories of starting": Understanding the complex contexts of opioid misuse initiation.

Background: The impacts of opioid use disorder and opioid-involved overdose are known, but less is known about the contexts in which people first misuse opioids, and the motivations for continued misuse. Methods: In-depth interviews with 26 individuals in Allegheny County, Pennsylvania with current or past histories of opioid misuse were conducted. Narratives were analyzed to understand the circumstances and influences contributing to initial and continued misuse of opioids. Results: Participants described social and familial contexts that normalized or accepted opioid misuse-this often included their own use of other illicit substances prior to initiating opioids. Participants also described initial use of opioids as related to efforts to cope with physical pain. They also described recognizing and then seeking psychological/emotional benefits from opioids. All three of these themes often overlapped and intersected in these stories of starting opioid misuse. Conclusions: Opioid misuse stemmed from complex interacting influences involving coping with physical and psychological pain, perception that opioids are needed to feel "normal", and acceptance or normalization of opioid use. This suggests a multi-pronged approach to both prevention and treatment are needed.

Vital Signs: Characteristics of Drug Overdose Deaths Involving Opioids and Stimulants - 24 States and the District of Columbia, January-June 2019.

INTRODUCTION: Provisional estimates indicate that drug overdose deaths increased in 2019 after a slight decrease in 2018. In 2018, overdose deaths primarily involved opioids, with continued increases in deaths involving illicitly manufactured fentanyls (IMFs). Deaths involving stimulants such as cocaine and methamphetamine are also increasing, mainly in combination with opioids. METHODS: CDC analyzed data on drug overdose deaths during January-June 2019 from 24 states and the District of Columbia (DC) in the State Unintentional Drug Overdose Reporting System to describe characteristics and circumstances of opioid- and stimulant-involved overdose deaths. RESULTS: Among 16,236 drug overdose deaths in 24 states and DC, 7,936 (48.9%) involved opioids without stimulants, 5,301 (32.6%) involved opioids and stimulants, 2,056 (12.7%) involved stimulants without opioids, and 943 (5.8%) involved neither opioids nor stimulants. Approximately 80% of overdose deaths involved one or more opioid, and IMFs were involved in three of four opioid-involved overdose deaths. IMFs, heroin, cocaine, or methamphetamine (alone or in combination) were involved in 83.8% of overdose deaths. More than three in five (62.7%) overdose deaths had documentation of at least one potential opportunity for overdose prevention intervention. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Identifying opportunities to intervene before an overdose death and implementing evidence-based prevention policies, programs, and practices could save lives. Strategies should address characteristics of overdoses involving IMFs, such as rapid overdose progression, as well as opioid and stimulant co-involvement. These efforts should be complemented by efforts to prevent initiation of prescription opioid and stimulant misuse and illicit drug use.

Opioid withdrawal symptoms, a consequence of chronic opioid use and opioid use disorder: Current understanding and approaches to management.

WHAT IS KNOWN AND OBJECTIVE: Opioid use in the United States has reached unprecedented-some would even say crisis-levels. Although many individuals use opioid drugs as part of legitimate pain management plans, a significant number misuse prescription or illicit opioids. With regular opioid use, individuals develop tolerance and physical dependence; both are predictable, physiologic responses to repeated opioid exposure. However, a substantial number of individuals who misuse opioids will develop opioid use disorder (OUD), a complex, primary, chronic, neurobiological disease rooted in genetic, environmental and psychosocial factors. This article discusses OUD, opioid receptor physiology, and opioid withdrawal symptomatology and pathophysiology, as well as current treatment options available to reduce opioid withdrawal symptoms in individuals with physical dependence and/or OUD. METHODS: The research articles regarding OUD and its management have been reviewed thoroughly based on a PubMed literature search using keywords related to opioid dependence, its pathophysiology and current treatment strategies. RESULTS AND DISCUSSION: Tolerance/physical dependence and the behavioural characteristics associated with OUD reflect complex neurobiologic adaptations in several major systems of the brain, including the locus ceruleus and mesolimbic systems. Physical dependence is responsible for the distressing withdrawal symptoms individuals experience upon abrupt cessation or rapid dose reduction of exogenous opioids. Opioid withdrawal symptoms are a key driver behind continued opioid use, and a barrier to opioid discontinuation. Several opioid-based medications are available to treat patients with OUD; these treatments can diminish opioid withdrawal symptoms and cravings as well as block opioid effects in the event of relapse. Additionally, non-opioid drugs may be used during acute detoxification to help alleviate opioid withdrawal symptoms. WHAT IS NEW AND CONCLUSION: The opioid crisis has produced many challenges for physicians, one being the need to determine which patients would benefit most from maintenance therapy and which may be candidates for opioid discontinuation. In addition to summarizing current understanding of OUD, we provide a new algorithm for determining the need for continued opioid use as well as examples of situations where management of opioid withdrawal symptoms is indicated.

Association of insulin-manipulation and psychiatric disorders: A systematic epidemiological evaluation of adolescents with type 1 diabetes in Austria.

BACKGROUND/OBJECTIVE: The aim of this study was to systematically assess the association of insulin-manipulation (intentional under- and/or overdosing of insulin), psychiatric comorbidity and diabetes complications. METHODS: Two diagnostic interviews (Diabetes-Self-Management-Patient-Interview and Children's-Diagnostic-Interview for Psychiatric Disorders) were conducted with 241 patients (age 10-22) with type 1 diabetes (T1D) from 21 randomly selected Austrian diabetes care centers. Medical data was derived from medical records. RESULTS: Psychiatric comorbidity was found in nearly half of the patients with insulin-manipulation (46.3%) compared to a rate of 17.5% in patients, adherent to the prescribed insulin therapy. Depression (18.3% vs 4.9%), specific phobia (21.1% vs 2.9%), social phobia (7.0% vs 0%), and eating disorders (12.7% vs 1.9%) were elevated in patients with insulin-manipulation. Females (37.7%) were more often diagnosed (P = 0.001) with psychiatric disorders than males (18.4%). In females, the percentage of psychiatric comorbidity significantly increased with the level of non-adherence to insulin therapy. Insulin-manipulation had an effect of +0.89% in HbA1c (P = <0.001) compared to patients adherent to insulin therapy, while there was no association of psychiatric comorbidity with metabolic control (HbA1c 8.16% vs 8.12% [65.68 vs 65.25 mmol/mol]). Ketoacidosis, severe hypoglycemia, and frequency of outpatient visits in a diabetes center were highest in patients with insulin-manipulation. CONCLUSIONS: This is the first study using a systematic approach to assess the prevalence of psychiatric disorders in patients who do or do not manipulate insulin in terms of intentional under- and/or overdosing. Internalizing psychiatric disorders were associated with insulin-manipulation, especially in female patients and insulin-manipulation was associated with deteriorated metabolic control and diabetes complications.

Prescription Opioid Misuse After a Recent Sexual Assault: A Randomized Clinical Trial of a Video Intervention.

BACKGROUND AND OBJECTIVES: Prescription opioid (PO) misuse is increasing and is associated with overdose. Individuals who experienced a recent sexual assault are at risk for increased substance use, yet limited interventions target PO misuse after sexual assault. The current study examined the efficacy of video interventions on PO misuse after sexual assault. METHODS: Adolescent girls and women (n = 154) were recruited in the context of a sexual assault medical forensic exam in the emergency department. Effects of a prevention of post-rape stress (PPRS) video and a pleasant imagery and relaxation instruction (PIRI) video were compared with treatment as usual (TAU) during a sexual assault medical forensic exam on PO misuse. Participants reported if they had used POs for non-medical purposes since the sexual assault at 1.5 month follow-up. RESULTS: Results from a logistic regression analysis indicated that participants with a prior sexual assault were less likely to misuse prescription opioids 1.5 months after the assault in the PIRI condition compared with TAU. There were no main effects for video condition and no interactions for the PPRS condition on PO misuse. DISCUSSION AND CONCLUSIONS: Providing the PIRI video, or teaching other types of mindfulness or relaxation exercises, may be warranted as a secondary prevention for individuals during the sexual assault medical forensic exam for those with a prior sexual assault history. SCIENTIFIC SIGNIFICANCE: This research provides an initial examination of the impact of mindfulness skills recently after traumatic event exposure on PO misuse. (Am J Addict 2019;28:376-381).

Integrating Public Health and Health Care Strategies to Address the Opioid Epidemic: The Oregon Health Authority's Opioid Initiative.

CONTEXT: Oregon is experiencing an opioid overdose epidemic, similar to the United States as a whole. To address this crisis, the Oregon Health Authority (OHA) implemented a strategic Opioid Initiative, convening stakeholders and integrating public health and health care system activities across sectors. Recent data indicate progress: from 2015 to 2016, Oregon had the sharpest decline in prescription opioid overdose deaths of any state. PROGRAM: The Opioid Initiative, launched in 2015, focuses on integrating efforts to improve patient care and safety, and population health, by increasing access to nonopioid pain treatment, supporting medication-assisted treatment and naloxone access for people taking opioids, decreasing opioid prescribing, and using data to inform policies and interventions. IMPLEMENTATION: Four OHA projects highlight the integration: (1) a Medicaid Coordinated Care Organization Performance Improvement Project focused on decreasing risky opioid prescribing; (2) Health Evidence Review Commission guidelines that set coverage standards for opioid and nonopioid back pain treatments for Medicaid recipients; (3) statewide opioid prescribing guidelines; and (4) an opioid data dashboard. Each project involves a partnership between governmental public health, public and private health care systems, and external stakeholders. PROGRESS: From 2015 to 2017, the number of Oregonians on 90 or more Morphine Equivalent Doses (MEDs) decreased by 37%, from 11.1 per 1000 residents quarterly to 7.0 per 1000 residents quarterly. Prescription opioid overdose deaths decreased 20% from 4.5 per 100 000 in 2015 to 3.6 per 100 000 in 2016. Within the Medicaid population, the percentage of clients on 120 or more MEDs for 30 consecutive days decreased 27%, from 2.3% in December 2015 to 1.6% in September 2017. DISCUSSION: Oregon's integrated approach to address the opioid crisis spans public health and health care systems, engages key stakeholders, and uses data and evidence to inform policies. The progress to date is promising and may assist other states seeking to identify effective strategies to decrease opioid prescribing, misuse, and overdose.

Potentially inappropriate medication use in elderly non-Hodgkin lymphoma patients is associated with reduced survival and increased toxicities.

Survival outcomes for elderly lymphoma patients are disproportionally inferior to those of younger patients. We examined medication usage at diagnosis for 171 elderly patients (median age 70 years) with aggressive non-Hodgkin lymphoma treated between 2009 and 2014. At least one potentially inappropriate medication was used in 47% of patients according to the Beers Criteria, 59% experienced treatment delays and/or dose reduction and 65% experienced ≥ grade 3 treatment-related toxicities. We report here for the first time that potentially inappropriate medication use was associated with reduced progression-free survival and overall survival, and increased ≥ grade 3 treatment-related toxicities in multivariate analysis.

Prescription Opioid Use is Associated with Virologic Failure in People Living with HIV.

Prescription opioid misuse is a rising epidemic in the U.S., and people living with HIV are at increased risk. We assessed the association between prescription opioid use and virologic failure in HIV+ patients in the South Texas HIV Cohort. We found prescription opioid use was significantly associated with virologic failure, after adjustment for age, race, gender, insurance status, years living with HIV, reported HIV risk factor, chronic hepatitis C virus infection, current substance abuse, and care engagement. These findings suggest that opioid analgesic use may have negative consequences beyond misuse in people living with HIV.

Cutaneous refractile foreign body microemboli with intravascular injection of oral medication.

Injection drug abuse (IDA) is known to cause a spectrum of systemic and cutaneous complications. Despite the increasing incidence of IDA around the world, there is a paucity of literature discussing cutaneous complications from a dermatopathologic perspective. We present a case of a 35-year-old male with a complex medical history of Von Willebrand disease, Beçhet disease and diverticular disease. Following a sigmoidectomy/colostomy for diverticular perforation, he presented with fever and an indurated right arm displaying livedoid purpura. The right distal fingertips showed purpura with focal ulceration. A punch biopsy of the right wrist did not show evidence of inflammatory vasculitis or pyogenic infection, but instead showed a focus of polarizing, refractile material occluding a dilated arterial lumen within the mid-dermis. The patient admitted to injecting a suspension of crushed ondansetron (Zofran) tablets into the antecubital area to control post-operative nausea. It is known that direct intravascular injection of foreign material can cause distal ischemia and necrosis, either by local vasoconstriction, thrombosis, or formation of microemboli, as in this patient. Our objective is to bring awareness to this rarely reported phenomenon, and to raise clinical suspicion for IDA when confronted with such a unique vasculopathic pattern.

Prescription opioid medication misuse among university students.

BACKGROUND AND OBJECTIVES: Prescription opioid misuse is an established problem in the United States. Less information is known regarding the clinical and cognitive characteristics of prescription opioid misusers, specifically in a college age population. This study sought to characterize individuals who misuse prescription opioids and the differences between current, past and non-misusers. METHODS: A 156-item survey was administered to over 9,449 university students at a large, public Midwestern university. Survey questions obtained demographic information, self-reported grade point average, sexual behavior, mental health characteristics, and substance use. Participants also completed assessments that asked questions regarding impulsivity, mental health, substance use, and other impulsive behaviors including gambling and sexual activity. 3,522 students completed the survey and were included in the analysis. RESULTS: Of this group, 2.2% reported misusing prescription opioids in the last 12 months and another 5.3% reported misusing prescription opioids previously but not in the past year. This study found prescription opioid misusers to be more likely to live off campus, have a lower GPA, and exhibit increased impulsivity. Prescription opioid misusers were also more likely to report earlier age of sexual activity and were less likely to use barrier protection during sexual activity. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This study identifies a number of risk factors for those misusing prescription opioids that can be used to develop and refine prescription opioid misuse screening tools for university health centers. It also identifies a number of concurring behaviors that can simultaneously be addressed when prescription opioid misusers are identified. (Am J Addict 2018;XX:1-7).

Adult consequences of prenatal drug exposure.

Maternal drug use is not new but over the last few decades, the number of mothers using drugs of addiction has escalated to epidemic levels. These drugs are both legal (e.g. prescription medication) and illegal (e.g. heroin) and all will cross the placental barrier into the developing infant. The most immediate and obvious consequence of intra-uterine drug exposure is newborn withdrawal or the Neonatal Abstinence Syndrome (NAS) which is now, with prompt recognition and treatment, an uncommon cause of neonatal death. Thousands (if not millions) of adults most likely would have had a history of passive drug exposure during gestation and the outcomes of these people are unknown. Most are physically healthy and do not need extra medical attention but the effects of prenatal drug exposure may be subtle and extensive. Drug-use disorders are accompanied by a myriad of other adverse problems, including poverty, mental and physical health problems and inadequate parenting ability that may compound the negative effects of drugs. Emerging data suggest that vulnerability to health and neurocognitive issues are pervasive and long-lasting as are lifestyle issues. This review will address current evidence in this area and highlight the knowledge gaps that must be addressed in order to optimise the outcomes for this vulnerable and marginalised but rapidly expanding population of adults.

Abuse liability assessment for biologic drugs - All molecules are not created equal.

The development of novel drug candidates involves the thorough evaluation of potential efficacy and safety. To facilitate the safety assessment in light of global increases in prescription drug misuse/abuse, health authorities have developed guidance documents which provide a framework for evaluating the abuse liability of candidate therapeutics. The guidances do not distinguish between small molecules and biologics/biotherapeutics; however, there are key differences between these classes of therapeutics which are important drivers of concern for abuse. An analysis of these properties, including ability to distribute to the central nervous system, pharmacokinetic properties (e.g., half-life and metabolism), potential for off-target binding, and the physiochemical characteristics of biologic drug products suggests that the potential for abuse of a biologic is limited. Many marketed antibodies and recombinant proteins have been associated with adverse effects such as headache and dizziness. However, biologics have not historically engendered the rapid-onset psychoactive effects typically present for drugs of abuse, thus further underscoring their low risk for abuse potential. The factors to be taken into consideration before conducting nonclinical abuse liability studies with biologics are described herein; importantly, the aggregate assessment of these factors leads to the conclusion that abuse liability studies are unlikely to be necessary for this class of therapeutics.

Risk of opioid misuse in chronic non-cancer pain in primary care patients - a cross sectional study.

BACKGROUND: Efforts to improve treatment of pain using opioids have to adequately take into account their therapeutic shortcomings which involve addictiveness. While there are no signs of an "opioid epidemic" in Germany similar to that in the US, there is little data on the prevalence of prescription opioid misuse and addiction. Therefore, our objective was to screen primary care patients on long-term opioid therapy for signs of misuse of prescription opioids. METHODS: We recruited 15 GPs practices and asked all patients on long-term opioid therapy (> 6 months) to fill out a questionnaire including the "Current Opioid Misuse Measure" (COMM®), a self-report questionnaire. Patients with a malignant disease were excluded. RESULTS: N = 91 patients participated in the study (response rate: 75.2%). A third (31.5%) showed a positive COMM® - Score which represents a high risk of aberrant drug behaviour. A positive COMM® - Score showed a statistically significant correlation with a lifetime diagnosis of depression and neck pain. CONCLUSIONS: While Germany does not face an "opioid eoidemic", addictiveness of opioids should be considered when using them in chronic non-tumor pain. In our study population, almost every third patient was at risk and should therefore be followed up closely. Co-prevalence of depression is a significant issue and should always be screened for in patients with chronic pain, especially thus with aberrant drug behaviour.

A community pharmacy intervention for opioid medication misuse: A pilot randomized clinical trial.

OBJECTIVES: Community pharmacy continues to play a crucial role in the national response to the opioid epidemic. The purpose of this article is to describe the protocol for a pilot study that is examining the feasibility and acceptability of the Motivational Intervention-Medication Therapy Management (MI-MTM) model. This study also examines the preliminary clinical effect of MI-MTM for improving opioid medication misuse and patient activation in self-management of health conditions that increase risk for misuse. DESIGN: MI-MTM is a pharmacy-based integrated care model made up of 4 evidence-based practices: medication therapy management; brief motivational intervention; patient navigation; and naloxone training and referral. To test MI-MTM compared with Standard Medication Counseling (SMC), we are conducting a 2-group randomized single-blinded controlled trial with assessments at 3 time points. SETTING AND PARTICIPANTS: The study is being conducted within a western Pennsylvania university-based community pharmacy with 46 patients with opioid misuse (MI-MTM = 23; SMC = 23). MAIN OUTCOME MEASURES: Feasibility will be measured by capturing patient completion rate of MI-MTM sessions. Acceptability will be measured by administering satisfaction surveys regarding pharmacist and patient navigator services. Acceptability will also be captured by conducting intensive qualitative interviews. Preliminary effect of the intervention on misuse will be measured with the use of the Prescription Opioid Misuse Index and the Opioid Compliance Checklist. Activation in self-management will be measured with the use of the Patient Activation Measure. RESULTS: This project is currently recruiting, and results are to come. CONCLUSION: This study is the first in the United States to implement an evidence-based integrated behavioral intervention into the community pharmacy setting to address opioid medication misuse among pharmacy patients. The results of this study will provide necessary foundational data that allow further testing of this intervention model in a larger trial.

Antibiotic use and abuse: a threat to mitochondria and chloroplasts with impact on research, health, and environment.

Recently, several studies have demonstrated that tetracyclines, the antibiotics most intensively used in livestock and that are also widely applied in biomedical research, interrupt mitochondrial proteostasis and physiology in animals ranging from round worms, fruit flies, and mice to human cell lines. Importantly, plant chloroplasts, like their mitochondria, are also under certain conditions vulnerable to these and other antibiotics that are leached into our environment. Together these endosymbiotic organelles are not only essential for cellular and organismal homeostasis stricto sensu, but also have an important role to play in the sustainability of our ecosystem as they maintain the delicate balance between autotrophs and heterotrophs, which fix and utilize energy, respectively. Therefore, stricter policies on antibiotic usage are absolutely required as their use in research confounds experimental outcomes, and their uncontrolled applications in medicine and agriculture pose a significant threat to a balanced ecosystem and the well-being of these endosymbionts that are essential to sustain health.

Motives for Prescription Stimulant Misuse in a College Sample: Characteristics of Users, Perception of Risk, and Consequences of Use.

BACKGROUND: Prescription stimulant misuse is increasingly prevalent in college populations, with some misuse estimates over 40%. Stimulant use is associated with a variety of health and psychological problems. Motives for use may provide insight into problematic trajectories. OBJECTIVES: The purpose of the current study was to evaluate characteristics of users and motives for prescription stimulant misuse in a large southeastern university. METHOD: College students reported on prescription stimulant use, motives for use, consequences associated with use, perceptions of risk, and social norms. We specifically elicited participation from prescription stimulant misusers. Of the 199 participants, 86 reported misusing prescription stimulants in the past 60 days. We assessed motives for use, rates of substance use, risk perception, normative beliefs, and consequences associated with use. We evaluated differences between misusers and non-misusers, differentiate motives subscales, and identify relationships between motives subscales, rates of use, and consequences. RESULTS: Misusers used more alcohol and other drugs, held different normative beliefs regarding stimulants, and had lower risk perceptions than non-misusers. We evaluated seven motives subscales among misusers: coping, social, enhancement, expansion, conformity, academic performance, and weight loss. Enhancement, social, weight loss, and expansion scales were correlated with negative consequences, while social motives were correlated with use. Results from regression analyses revealed positive associations between weight and expansion with negative consequences, and a negative association between conformity and consequences. Conclusions/Importance:Motives for prescription stimulant use and user characteristics may provide insight into prevention and treatment. Continued work is needed to refine item content and replicate findings.

Unilateral hemorrhagic macular infarction associated with marijuana, alcohol and antiepileptic drug intake.

A 55-year-old male presented with a complaint of a painless and sudden loss of vision in the right eye. Fundus photography revealed loss of transparency and edema in the central macular region. Optical coherence tomography showed increased reflectivity and diffused swelling in the inner retinal layers. Fluorescein angiography revealed a large area of capillary non-perfusion with a pronounced hypofluorescent area with distinct borders. To our knowledge, this is the first report of a hemorrhagic macular infarction associated with marijuana and pregabalin misuse.