Chronic Marijuana Research Articles

Cannabinoids Hyperemesis Syndrome

Introduction: Cannabinoid hyperemesis syndrome (CHS) is characterized by chronic marijuana use, cyclic vomiting, abdominal pain, and compulsive need to take hot showers. This syndrome is an episodic, recurrent disorder in which three phases have been described: a prodromal, hyper-emetic, and a recovery phase with resolution of symptoms upon cessation of marijuana use. Case Presentation: We report a case of a 33-year- old female with long history of cannabinoid use who presented to emergency department complaining of abdominal pain, nausea and vomiting for 3 days. She reported having recurrent similar episodes for the last 4 years, usually every 3 - 4 months. An extensive gastrointestinal evaluation was done before, but failed to identify a clear cause for her symptoms. Based on the diagnostic criteria for CHS, the diagnosis of CHS was made. After discharge the patient had a symptom-free period with the cessation of marijuana use. However, she relapsed later and her symptoms returned. Conclusions: This case illustrates the importance of having a high index of suspicion for CHS in patients with history of cannabis use, since earlier recognition of can help reduce unnecessary workups, doctor visits, and hospital admissions.

Depression, young age, chronic marijuana use, and interepisodic symptoms predict psychological distress in patients with cyclic vomiting syndrome.

Cyclic vomiting syndrome (CVS) is often triggered by stress. Patients report high degrees of psychological distress due to CVS, but there is limited data on factors associated with psychological distress. We sought to determine the degree of psychological distress and its correlation with clinical characteristics in CVS. The Brief Symptom Inventory (BSI), a validated tool to determine psychological distress, was administered prospectively to patients. The control population consisted of 719 normal subjects. Student's t test was used to compare means, and logistic regression analysis was performed to identify predictors of a GSI score ≥63, indicating high degrees of psychological distress. Scores for the regression predictors were calculated using the maximum likelihood estimate for the logistic regression model and was called the DAME score (depression, age 25-35, chronic marijuana use, and interepisodic GI symptoms). Of 87 patients, 60% were female, 92% were caucasian, and mean age was 37years. Forty-one percent of patients had high degrees of psychological distress with the highest scores for somatization. Independent predictors of psychological distress included depression, young age (25-35years), chronic marijuana use, and interepisodic dyspepsia (called the DAME score). A score of ≥7 accurately predicted psychological distress in >88% of patients. Psychological distress is common in CVS and can be predicted accurately using our proposed DAME score. Whether psychological distress is a cause or an effect of CVS needs to be determined. Addressing psychological distress can potentially improve overall healthcare outcomes in CVS.

Associations Between Microbiota, Mitochondrial Function, and Cognition in Chronic Marijuana Users.

Marijuana (MJ) use is associated with cognitive deficits. Both mitochondrial (mt) dysfunction and gut dysbiosis also affect cognition. We examined whether cognition is related to peripheral blood mononuclear cells' (PBMCs) mt function and fecal microbiota in chronic MJ users. Nineteen chronic MJ users and 20 non-users were evaluated using the Cognition Battery in NIH Toolbox, their mt function for ATP production, and basal and maximal respirations were measured in PBMCs using the Seahorse XFe96 Analyzer, and the abundances of Prevotella and Bacteroides (associated with plant-based and animal product-based diet, respectively) were calculated from stool microbiota analysis. Average Prevotella:Bacteroides ratio was ~13-fold higher in nonusers than users. Lifetime MJ use correlated inversely with Prevotella:Bacteroides ratio (p=0.05), mt function (p=0.0027-0.0057), and Flanker Inhibitory Control and Attention (p=0.041). Prevotella abundance correlated positively, while Bacteroides abundance correlated inversely, with mt function across all participants (p=0.0004-0.06). Prevotella abundance also correlated positively with scores of Fluid Cognition, Flanker Inhibitory Control and Attention, List Sorting, and Dimension Change Card Sort in MJ users, but not in non-users (interaction-p=0.018-0.05). Similarly, mt function correlated positively with scores of Fluid Cognition and Flanker Inhibitory Control and Attention in MJ users, but not in non-users (interaction-p=0.0018-0.08). These preliminary findings suggest that MJ use is associated with alterations of gut microbiota and mt function, which may further contribute to cognitive deficits. We posited that MJ-associated low vegetable/fruit intake may contribute to these changes. Future studies are needed to delineate the relationships among diet, microbiota, mt function, and cognition in MJ users.

Adolescent THC Exposure Causes Enduring Prefrontal Cortical Disruption of GABAergic Inhibition and Dysregulation of Sub-Cortical Dopamine Function

Chronic adolescent marijuana use has been linked to the later development of psychiatric diseases such as schizophrenia. GABAergic hypofunction in the prefrontal cortex (PFC) is a cardinal pathological feature of schizophrenia and may be a mechanism by which the PFC loses its ability to regulate sub-cortical dopamine (DA) resulting in schizophrenia-like neuropsychopathology. In the present study, we exposed adolescent rats to Δ-9-tetra-hydrocannabinol (THC), the psychoactive component in marijuana. At adulthood, we characterized the functionality of PFC GABAergic neurotransmission and its regulation of sub-cortical DA function using molecular, behavioral and in-vivo electrophysiological analyses. Our findings revealed a persistent attenuation of PFC GABAergic function combined with a hyperactive neuronal state in PFC neurons and associated disruptions in cortical gamma oscillatory activity. These PFC abnormalities were accompanied by hyperactive DAergic neuronal activity in the ventral tegmental area (VTA) and behavioral and cognitive abnormalities similar to those observed in psychiatric disorders. Remarkably, these neuronal and behavioral effects were reversed by pharmacological activation of GABAA receptors in the PFC. Together, these results identify a mechanistic link between dysregulated frontal cortical GABAergic inhibition and sub-cortical DAergic dysregulation, characteristic of well-established neuropsychiatric endophenotypes.

Pharmacologic Implications of Marijuana Use During Pregnancy

Marijuana is the most commonly used recreational drug in the United States, including among women of childbearing age and women who are pregnant. Changing legal statutes that allow for the use of medical marijuana and the decriminalization of marijuana for personal use reflect more permissive societal views on the use of this drug. Active compounds in marijuana cross the placenta rapidly and are excreted in breast milk. Results of studies of the effects of marijuana on a developing fetus and neonate are conflicting, but researchers have identified chronic marijuana exposure as a risk factor for preterm birth and small-for-gestational-age infants. This article reviews the pharmacology of marijuana and discusses implications for nurses who work with women of childbearing age.

Idiopathic nodular glomerulosclerosis in a chronic marijuana user; a case report and review of the literature

Background: Nodular glomerulosclerosis is a characteristic histological finding of diabetic nephropathy (DN) with thickened glomerular basement membrane (GBM) and hyalinized arterioles. Idiopathic nodular glomerulosclerosis (ING), a rare distinct clinicopathologic entity, is the term used to denote classic DN confirmed by light microscopy, immunofluorescence, and electron microscopy in the absence of diabetes mellitus (DM). ING has been linked to heavy tobacco smoking, chronic hypertension, obesity and insulin resistance. Its association with marijuana use is unknown. Case Presentation: We report a case of biopsy-proved ING in the absence of pre-existing history of DM and heavy smoking. This report addresses the possible accentuation of tobacco use risk by marijuana. Conclusions: This report addresses the possible accentuation of tobacco use risk by marijuana.

Cannabinoids and Symptomatic Bradycardia

Cannabinoids, the bioactive components of marijuana, have adverse cardiovascular consequences, including symptomatic sinus bradycardia, sinus arrest and ventricular asystole. Physicians should be aware of these deleterious consequences which can appear in otherwise healthy persons who are chronic marijuana users.

CD8+ lymphocytes and Cd14highCd16low monocytes in chronic marijuana using HIV patients

CD8+ lymphocytes and Cd14highCd16low monocytes in chronic marijuana using HIV patients

SPONTANEOUS PNEUMOMEDIASTINUM IN A YOUNG MALE SECONDARY TO CHRONIC MARIJUANA ABUSE

Illicit drug use is emerging as a global health problem, also leading to deteriorated socioeconomic condition. Cannabis (Marijuana) is used throughout the world, and its use is increasing. Marijuana is associated with airway inflammation leading to pneumothorax, pneumomediastinum. It also predisposes to lung cancer. Here, we are presenting a young male presented with a cough and progressively worsening dyspnea. Imaging showed pneumomediastinum. The patient revealed chronic marijuana use for many years. Clinicians treating young adults and adolescents should be aware of the entity associated with illicit drug use, and thorough clinical and social history is warranted for early diagnosis of the perforated organ.

Violence, Trauma, Mental Health, and Substance Use Among Homeless Youth Juggalos.

Insane Clown Posse is a musical duo whose fans are known as Juggalos. Many homeless youths (HY) identify as Juggalos, most likely because the group's music embraces poverty and being an outsider in mainstream society. Juggalos are stereotyped as being violent, undereducated, poor, racist, crime-committing youth, and in 2011 the FBI officially labeled Juggalos as a gang. However, little is known about the intersection of HY and Juggalos. A convenience sample of Los Angeles-area, drop-in service-seeking HY completed a self-administered questionnaire (N = 495). In the sample, 15 % of HY identified as Juggalos. Juggalo-identifying youth were more likely to have experienced childhood trauma, including physical and sexual abuse and witnessing community violence. Multivariable models revealed that identifying as a Juggalo was associated with increased odds of recent methamphetamine use, ecstasy use, chronic marijuana use, and prescription drug misuse. Juggalos were also more likely to experience suicidal ideation, attempt suicide, recently engage in interpersonal violence, become injured during a fight, and have unprotected sex. In conclusion, Juggalos constitute a unique subpopulation of HY. Implications for Juggalo-specific trauma-informed services, rather than punitive, are discussed as well as the potential for future research regarding resiliency associated with Juggalo identification.

Adult Cyclic Vomiting Syndrome Is Treatable and Curable

Introduction: Cyclic Vomiting Syndrome (CVS) in adults is underdiagnosed because it is not well recognized by physicians although it accounts for up to 20% of patients referred to a GI practice for evaluation of unexplained vomiting and abdominal pain. Goals of therapy are to induce remission while also addressing the predisposing “trigger” factors. The purposes of this study are to provide an analysis of the clinical profile, treatment responses, and outcomes based on managing adult CVS at a GI motility center. Methods: Our adult CVS database identified 18 patients, 10 female, of ages ranging from 22-60, who were initially diagnosed at our center, received treatment, and had long term follow up of 1 to 4 years by one of the authors. Results: Onset of symptoms ranged from 1-15 years prior to diagnosis (mean of 4). The mean number of yearly ER visits or hospitalizations was 5.8. Weight loss ranged from 5-50 pounds. Ten patients underwent a 4 hour standardized radionuclide gastric emptying test: 6 had rapid emptying and. Six major “triggers” were identified (some patients having >1): anxiety in 17, post-traumatic stress disorder in 2, migraines in 5, chronic marijuana use in 5, poorly controlled diabetes in 5, and menses in 4. All patients were treated with tricyclic antidepressants. Amitriptyline was the first choice, starting at 10mg at night, increasing by 10mg every 2-3 weeks until CVS improved. Two patients were switched to doxepin due to side effects; their max doses were 100mg and 200mg. At the same time the “trigger” factors were aggressively addressed. With this treatment strategy 4 patients (22%) were able to stop their CVS medications and have remained asymptomatic for over 1 year. In addition, 11 patients (61%) responded remarkably with a reduction in the mean number of annual ER visits or hospitalizations from 5.8 to 0.6 and were fully functional. Three patients (17%) reported ongoing, approximately monthly, episodes and had unresolved trigger factors and medication noncompliance. Conclusion: 1) Adult CVS is a treatable and reversible entity; 2) The treatment consisting of high dose TCA & addressing the “trigger factors” was able to prevent cycles in 83% of patients, including 22% that were effectively cured and able to taper off medications without recurrence; 3) The approximately 17% of patients who have ongoing cycles require better control of the predisposing factors as well as reinforcing compliance with the treatment regimen.

ISMP Adverse Drug Reactions: Chronic Marijuana Use Associated With Recurrent Diabetic Ketoacidosis Lamotrigine-Induced Cataplexy Trimethoprim-Sulfamethoxazole-Induced Hyponatremia Ziprasidone-Induced Sleepwalking and Sleep-Related Eating Metabolic Acidosis Associated With Acetaminophen.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Comorbid trajectories of substance use as predictors of Antisocial Personality Disorder, Major Depressive Episode, and Generalized Anxiety Disorder

ObjectiveTo determine longitudinal associations between patterns of comorbid cigarette, alcohol, and marijuana use and Antisocial Personality Disorder (ASPD), Major Depressive Episode (MDE), and Generalized Anxiety Disorder (GAD) in adulthood. MethodA random community-based sample [X̅ age=36.6 (SD=2.8)] from the Children and Adults in the Community Study, an on-going investigation of substance use and psychiatric disorders. Data were collected at six time waves. Conjoint trajectories of cigarette, alcohol, and marijuana use spanning adolescence to adulthood were determined; multivariable logistic regression analyses assessed associations between trajectory group membership and having ASPD, MDE, or GAD in adulthood. ResultsFive conjoint trajectory groups were obtained: HHH (chronic cigarette, alcohol, and marijuana use), DDD (delayed/late-starting cigarette, alcohol, and marijuana use), LML (low/no smoking, moderate alcohol use, occasional marijuana use), HMN (chronic smoking, moderate alcohol use, no marijuana use), and NON (occasional alcohol use only). Compared with members of the NON group, those in the HHH group had significantly greater odds for having ASPD (Adjusted Odds Ratio [AOR]=28.52, 95% Confidence Interval [CI]=9.44–86.17), MDE (AOR=2.67, 95% CI=1.14–6.26), and GAD (AOR=6.39, 95% CI=2.62–15.56). Members of the DDD, LML, and HMN groups had weaker and less consistent associations with the three psychiatric outcomes. ConclusionsIn a large, community-based sample, long-term concurrent use of more than one substance was associated with both externalizing and internalizing psychiatric disorders in adulthood. Prevention and treatment programs might target individuals in the community and general clinical populations with comorbid substance use, even if they haven't been identified as having a substance use disorder.

What Can Rats Tell Us about Adolescent Cannabis Exposure? Insights from Preclinical Research.

Marijuana is the most widely used drug of abuse among adolescents. Adolescence is a vulnerable period for brain development, during which time various neurotransmitter systems such as the glutamatergic, GABAergic, dopaminergic, and endocannabinoid systems undergo extensive reorganization to support the maturation of the central nervous system (CNS). ▵-9-tetrahydrocannabinol (THC), the psychoactive component of marijuana, acts as a partial agonist of CB1 cannabinoid receptors (CB1Rs). CB1Rs are abundant in the CNS and are central components of the neurodevelopmental changes that occur during adolescence. Thus, overactivation of CB1Rs by cannabinoid exposure during adolescence has the ability to dramatically alter brain maturation, leading to persistent and enduring changes in adult cerebral function. Increasing preclinical evidence lends support to clinical evidence suggesting that chronic adolescent marijuana exposure may be associated with a higher risk for neuropsychiatric diseases, including schizophrenia. In this review, we present a broad overview of current neurobiological evidence regarding the long-term consequences of adolescent cannabinoid exposure on adult neuropsychiatric-like disorders.

Endocannabinoid-related lipids are increased during an episode of cyclic vomiting syndrome.

The endocannabinoid system and the hypothalamic-pituitary-adrenal axis are important neuromodulators of nausea and vomiting. This led us to hypothesize that patients with cyclic vomiting syndrome (CVS) have lower serum endocannabinoids (eCBs) and higher salivary cortisol and alpha amylase. Serum eCBs and related lipids, N-oleoylethanolamine (OEA) and N-palmitoylethanolamide (PEA), and salivary cortisol, and alpha amylase (index of sympathetic nervous system activity) were measured in 22 CVS patients (age 40 ± 11, female = 17) in the well and sick phases and 12 matched controls (age 37 ± 12, female = 10). Contrary to our hypothesis, serum concentrations of the eCBs were not different among the study groups. However, serum concentrations of OEA and PEA were significantly higher during the sick than well phase in CVS patients (p = 0.001 and p = 0.04). There were positive correlations between serum PEA and nausea scores in the sick phase (Pearson's rho = 0.48, p = 0.036) and between serum OEA and poor sleep quality in patients (Pearson's rho = 0.7, p = 0.0005). Salivary cortisol and alpha amylase were not different between patients and controls, but subgroup analysis revealed that both were significantly higher in marijuana users compared to non-users during the sick phase (p = 0.04 and 0.03, respectively). These data demonstrate that eCB-related lipids, OEA and PEA, are mobilized in the sick phase of CVS and are positively correlated with several of the symptoms of a CVS episode. These data also suggest the hypothesis that chronic marijuana use results in enhanced stress responses during CVS.

A 21-year-old woman with right lower quadrant abdominal pain

This section features outstanding photographs of clinical materials selected for their educational value or message, or possibly their rarity. The images are accompanied by brief case reports (limit 2 typed pages, 4 references). Our readers are invited to sumit items for consideration. A 21-year-old woman presented to the emergency department with a 5-day history of periumbilical abdominal pain, which gradually migrated toward her right lower quadrant (RLQ). Associated symptoms included nausea, emesis, and constipation. She had a medical history significant for chronic nausea, anorexia, and marijuana abuse. Her obstetric background consisted of 3 gestations and 1 natural spontaneous vaginal delivery. This section features outstanding photographs of clinical materials selected for their educational value or message, or possibly their rarity. The images are accompanied by brief case reports (limit 2 typed pages, 4 references). Our readers are invited to sumit items for consideration.

Trajectories of marijuana use from adolescence to adulthood as predictors of unemployment status in the early forties.

To study the degree to which individuals in different trajectories of marijuana use are similar or different in terms of unemployment status at mean age 43. We gathered longitudinal data on a prospective cohort taken from a community sample (N = 548). Forty-nine percent of the original participants were females. Over 90% of the participants were white. The participants were followed from adolescence to early midlife. The mean ages of participants at the follow-up interviews were 14.1, 16.3, 22.3, 27.0, 31.9, 36.6, and 43.0, respectively. We used the growth mixture modeling (GMM) approach to identify the trajectories of marijuana use over a 29-year period. Five trajectories of marijuana use were identified: chronic users/decreasers (8.3%), quitters (18.6%), increasing users (7.3%), chronic occasional users (25.6%), and nonusers/experimenters (40.2%). Compared with nonusers/experimenters, chronic users/decreasers had a significantly higher likelihood of unemployment at mean age 43 (adjusted odds ratio = 3.51, 95% confidence interval = 1.13-10.91), even after controlling for the covariates. The results of the associations between the distinct trajectories of marijuana use and unemployment in early midlife indicate that it is important to develop intervention programs targeting chronic marijuana use as well as unemployment in individuals at this stage of development. Results from this study should encourage clinicians, teachers, and parents to assess and treat chronic marijuana use in adolescents.

Marijuana Use Predicts Cognitive Performance on Tasks of Executive Function.

Despite growing evidence that chronic marijuana use is associated with cognitive impairment, particularly when use is initiated at an early age, national trends demonstrate significant decreases in the perceived risk of marijuana corresponding with increased use, especially among youth. The current study assessed the impact of marijuana use on executive function and whether patterns of marijuana use, including earlier age at onset, higher frequency, and increased magnitude of use, predict impairment. Forty-four chronic, heavy marijuana smokers (37 male, 7 female) and 32 healthy, nonsmoking control participants (20 male, 12 female) recruited from the Greater Boston area completed two assessments of executive function: the Stroop Color Word Test and Wisconsin Card Sorting Test (WCST). Marijuana smokers had poorer executive function relative to control participants, a between-group difference that was primarily driven by individuals with early onset of marijuana use (before age 16; n = 21); significance remained even when controlling for frequency and magnitude of use. Further, earlier age at marijuana onset and increased marijuana use predicted poorer neurocognitive performance, and perseverative errors on the WCST significantly predicted marijuana group membership. These findings underscore the impact of early onset of marijuana use on executive function impairment independent of increased frequency and magnitude of use. In addition, poorer performance on the WCST may serve as a neuropsychological marker for heavy marijuana users. These results highlight the need for additional research to identify predictors associated with early marijuana use, as exposure to marijuana during a period of developmental vulnerability may result in negative cognitive consequences.

Cannabinoid Hyperemesis Syndrome

Cannabinoid hyperemesis is a relatively rare but significant adverse effect of chronic marijuana use characterized by severe, cyclic nausea, vomiting, and abdominal pain and marked by compulsive hot-water bathing for temporary symptom relief. A 37-year-old African American male with no significant medical history other than the habitual abuse of marijuana was admitted for intractable nausea, vomiting, and abdominal pain. With the exception of abdominal skin hyperpigmentation and scarring secondary to the direct application of heat through a heating pad, physical examination of the abdomen was unremarkable. Laboratory studies revealed a mild leukocytosis and acute renal dysfunction. All diagnostic examinations were found to be unremarkable or noncontributory to the patient's presenting state. Consistent with previous admissions, the patient's urine toxicology screening was found to be positive for marijuana. After several days of aggressive IV fluid hydration and as needed antiemetics and pain management, all laboratory studies and vital signs returned to baseline and the patient was subsequently discharged. Symptoms of cannabinoid hyperemesis resolve with cannabis cessation and recur when cannabis use is reinitiated, supporting an association between chronic use and cyclic vomiting. A Naranjo algorithm score of 5 revealed a probable incidence of cyclic vomiting associated with chronic cannabis abuse in our patient. Marijuana use, both legal and illegal, is becoming more prevalent in the United States. Given the nationwide increase in marijuana use for recreational and medical reasons, pharmacists and other health care providers should be aware of this interesting drug-induced phenomenon.

Sexual risk, substance use, mental health, and trauma experiences of gang-involved homeless youth

This study examined the associations of sexual risk behaviors, substance use, mental health, and trauma with varying levels of gang involvement in a sample of Los Angeles-based homeless youths. Data were collected from 505 homeless youths who self-reported various health information and whether they have ever identified as or been closely affiliated with a gang member. Multivariable logistic regression assessed associations of lifetime gang involvement with risk taking behaviors and negative health outcomes. Results revealed seventeen percent of youths have ever identified as a gang member and 46% as gang affiliated. Both gang members and affiliates were at greater risk of many negative behaviors than non-gang involved youths. Gang members and affiliates were more likely to report recent methamphetamine use, cocaine use, chronic marijuana use, having sex while intoxicated, and symptoms of depression, symptoms of posttraumatic stress disorder. They were also more likely to have experienced childhood sexual abuse and witnessing family violence. Gang members were more likely to ever attempt suicide, experience recent partner violence, and report physical abuse during childhood. Results suggest that lifetime gang involvement is related to a trajectory of negative outcomes and amplified risk for youths experiencing homelessness. Additionally, being closely connected to a gang member appears to have just as much as an impact on risk as personally identifying as a gang member. Given the lack of knowledge regarding the intersection between youth homelessness and gang involvement, future research is needed to inform policies and programs that can address the specific needs of this population.