Evaluation of the immune system status and hematological dyscrasias, among amphetamine and cannabis abusers at Eradah Hospital in Qassim, Saudi Arabia.

This cross-sectional study aims to evaluate the immune system status and hematological disturbances among individuals who abuse amphetamines and cannabis. Substance abuse, particularly of amphetamines and cannabis, has been associated with various adverse effects on the body, including potential impacts on the immune system and hematological parameters. However, limited research has been conducted to comprehensively assess these effects in a cross-sectional design. Additionally, fungal infections are on the rise internationally, and immune-compromised people are particularly susceptible. The study will recruit a sample of amphetamine and cannabis abusers (n = 50) at the Eradah Hospital in the Qassim Region of Buraydah and assess their sociodemographic and biochemical variables, including blood indices and differential WBC indices, liver, and kidney profiles. Additionally, 50 sputum samples in total were cultured for testing for fungus infections. To obtain the descriptive statistics, the data was imported into Microsoft Excel and subjected to statistical analysis using SPSS 22.0. Amphetamine and cannabis abuser's sociodemographic variables analysis observed that the majority (52%) were aged 18-30, with 56% in secondary school. Unemployment was a significant issue, and most had no other health issues. The majority (50%) had 5-10 years of abuse, while 32% had less than 5 years, and only 18% had been drug abusers for more than 10 years. There were significant changes (p < 0.001) in all different leukocyte blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Furthermore, a microscopic examination of blood films from individuals who misuse the combination of the medications "amphetamine and cannabis" reveals hazardous alterations in Neutrophils. Out of 50, 35 sputum samples showed positive growth on Sabouraud dextrose agar (SDA) with chloramphenicol antibiotic, indicating a unicellular fungal growth. The present study explores the immune system and hematological disturbances linked to amphetamine and cannabis abuse, providing insights into health risks and targeted interventions. The findings complement previous research on drug users' hematological abnormalities, particularly in white blood cells. Routine hematological tests help identify alterations in homeostatic conditions, improving patient knowledge and preventing major issues. Further research is needed on multi-drug abuse prevention, early detection, and intervention. The cross-sectional design allows for a snapshot of the immune system and hematological status among abusers, laying the groundwork for future longitudinal studies. Key Words: Drug Effect, Immunity, Epidemiology, Oxidative Stress, Inflammation.

The Link between Cannabis Use, Immune System, and Viral Infections.

Cannabis continues to be the most used drug in the world today. Research shows that cannabis use is associated with a wide range of adverse health consequences that may involve almost every physiological and biochemical system including respiratory/pulmonary complications such as chronic cough and emphysema, impairment of immune function, and increased risk of acquiring or transmitting viral infections such as HIV, HCV, and others. The review of published research shows that cannabis use may impair immune function in many instances and thereby exerts an impact on viral infections including human immune deficiency virus (HIV), hepatitis C infection (HCV), and human T-cell lymphotropic type I and II virus (HTLV-I/II). The need for more research is also highlighted in the areas of long-term effects of cannabis use on pulmonary/respiratory diseases, immune dysfunction and the risk of infection transmission, and the molecular/genetic basis of immune dysfunction in chronic cannabis users.

The Clinical Conundrum of Cannabis: Current Practices and Recommendations for Transplant Clinicians: An Opinion of the Immunology/Transplantation PRN of the American College of Clinical Pharmacy.

Cannabis, or marijuana, comprises many compounds with varying effects. It has become a treatment option for chronic diseases and debilitating symptoms, and evidence suggests that it has immunomodulatory and antiinflammatory properties. Transplant centers are more frequently facing issues about cannabis, as indications and legalization expand. As of February 2020, 33 states and the District of Columbia have legalized medical cannabis, and 14 have legalized recreational cannabis. Moreover, 8 states have passed legislation prohibiting the denial of transplant listing solely based on cannabis use. Studies demonstrate the potential for significant pharmacokinetic and pharmacodynamic interactions between cannabis and immunosuppression. Additionally, safety concerns include increased risk of myocardial infarction, ischemic stroke, tachyarrhythmias, malignancy, neurocognitive deficits, psychosis, other neuropsychiatric disorders, cannabis use disorder, respiratory symptoms, and infection. A recent retrospective database study found a negative association between documented cannabis use disorder and graft survival, but little additional evidence exists evaluating this relationship. In the absence of robust clinical data, transplant centers need a clear, reasoned, and systematic approach to cannabis. The results of our national survey, unfortunately, found little consensus among institutions. As both recreational and medicinal cannabis become more ubiquitous nationwide, transplant centers will need to develop comprehensive policies to address its use.

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.

Associations of first trimester co-use of tobacco and Cannabis with prenatal immune response and psychosocial well-being.

PURPOSE: This study aims to describe the association of first trimester co-use of tobacco and cannabis with maternal immune response and psychosocial well-being, relative to tobacco use only. METHODS: A preliminary midpoint analysis included 138 pregnant women with biologically verified tobacco use, 38 of whom (28%) also tested positive for recent cannabis use. Maternal perceived stress (Perceived Stress Scale), depressive symptoms (Edinburgh Postnatal Depression Scale), and serum immune markers (IL-1ß, IL-2, IL-6, IL-8, IL-10, TNFα, CRP, MMP8), were collected, although cytokine data were only available for 122 women. RESULTS: Participant average age was 29.1 years, approximately half had a high school education or less, and half were unemployed. Compared to tobacco only users, co-users were more likely to be non-White, younger and more economically disadvantaged. In the adjusted linear regression models, TNF-α levels were significantly lower among co-users relative to tobacco only users, after adjusting for age, race/ethnicity, body mass index and tobacco use group (tobacco cigarettes, electronic nicotine delivery devices [ENDS] or both). TNF-α was the only immune marker found to be significant in this analysis. Measured stress levels (M = 5.9, SD = 3.3; potential range 0-16) and depression scores (M = 7.8, SD = 5.8; potential range 0-30) were low across all participants and did not differ as a function of co-use. CONCLUSION: Preliminary results suggest women co-using during the first trimester exhibit decreased pro-inflammatory immune responsivity on one out of eight markers. Further research is needed to determine the impact of this immune modulation on fetal health outcomes and the unique contribution of cannabis.

Alcohol and cannabis use alter pulmonary innate immunity.

PURPOSE: Cannabis use is increasing due to recent legislative changes. In addition, cannabis is often used in conjunction with alcohol. The airway epithelium is the first line of defense against infectious microbes. Toll-like receptors (TLR) recognize airborne microbes and initiate the inflammatory cytokine response. The mechanism by which cannabis use in conjunction with alcohol affects pulmonary innate immunity mediated by TLRs is unknown. METHODS: Samples and data from an existing cohort of individuals with alcohol use disorders (AUDs), along with samples from additional participants with cannabis use alone and with AUD were utilized. Subjects were categorized into the following groups: no alcohol use disorder (AUD) or cannabis use (control) (n = 46), AUD only (n = 29), cannabis use-only (n = 39), and AUD and cannabis use (n = 29). The participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and airway epithelial brushings. We measured IL-6, IL-8, TNF⍺, and IL-10 levels in BAL fluid, and performed real-time PCR for TLR1-9 on the airway epithelial brushings. RESULTS: We found significant increases in TLR2 with AUD alone, cannabis use alone, and cannabis use with AUD, compared to control. TLR5 was increased in cannabis users compared to control, TLR6 was increased in cannabis users and cannabis users with AUD compared to control, TLR7 was increased in cannabis users compared to control, and TLR9 was increased in cannabis users compared to control. In terms of cytokine production, IL-6 was increased in cannabis users compared to control. IL-8 and IL-10 were increased in AUD only. CONCLUSIONS: AUD and cannabis use have complex effects on pulmonary innate immunity that promote airway inflammation.

Heavy Cannabis Use Associated With Reduction in Activated and Inflammatory Immune Cell Frequencies in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Individuals.

Background: Cannabis is a widely used drug in the United States, and the frequency of cannabis use in the human immunodeficiency virus (HIV)-infected population is disproportionately high. Previous human and macaque studies suggest that cannabis may have an impact on plasma viral load; however, the relationship between cannabis use and HIV-associated systemic inflammation and immune activation has not been well defined. Methods: The impact of cannabis use on peripheral immune cell frequency, activation, and function was assessed in 198 HIV-infected, antiretroviral-treated individuals by flow cytometry. Individuals were categorized into heavy, medium, or occasional cannabis users or noncannabis users based on the amount of the cannabis metabolite 11-nor-carboxy-tetrahydrocannabinol (THC-COOH) detected in plasma by mass spectrometry. Results: Heavy cannabis users had decreased frequencies of human leukocyte antigen (HLA)-DR+CD38+CD4+ and CD8+ T-cell frequencies, compared to frequencies of these cells in non-cannabis-using individuals. Heavy cannabis users had decreased frequencies of intermediate and nonclassical monocyte subsets, as well as decreased frequencies of interleukin 23- and tumor necrosis factor-α-producing antigen-presenting cells. Conclusions: While the clinical implications are unclear, our findings suggest that cannabis use is associated with a potentially beneficial reduction in systemic inflammation and immune activation in the context of antiretroviral-treated HIV infection.

Differential effects of self-reported lifetime marijuana use on interleukin-1 alpha and tumor necrosis factor in African American adults.

It is unknown how lifetime marijuana use affects different proinflammatory cytokines. The purpose of the current study is to explore potential differential effects of lifetime marijuana use on interleukin-1 alpha (IL-1α) and tumor necrosis factor (TNF) in a community based sample. Participants included 168 African American adults (51 % female, median age = 47 years). Upon study entry, blood was drawn and the participants completed questions regarding illicit drug use history whose answers were used to create three groups: lifetime non-drug users (n = 77), lifetime marijuana only users (n = 46) and lifetime marijuana and other drug users (n = 45). In the presence of demographic and physiological covariates, non-drug users were approximately two times more likely (AOR 2.73, CI 1.18, 6.31; p = .03) to have higher TNF levels than marijuana only users. Drug use was not associated with IL-1α. The influence of marijuana may be selective in nature, potentially localizing around innate immunity and the induction of cellular death.

Th17/Treg imbalance in opioids and cannabinoids addiction: relationship to NF-κB activation in CD4+ T cells.

Opioids are widely used for the treatment of severe pain. However, opioids, particularly morphine, is known to cause immunosuppression. This study investigated the impact of morphine and cannabinoids addiction on CD4+ T cell mediated immunity. We hypothesize that, accompanied immunosuppression is attributed to reduced T cell activation with an extent of affection to the cytoplasmic activity of the biologically active transcription factor nuclear factor-κB (NF-κB) which play crucial role in T-cell activation. A disturbance in cytokine balance, in particular, interleukin-17 (IL-17)/interleukin-10 (IL-10) production may also act as a mechanism of immunosuppression. Peripheral blood CD4+ T cells from 45 chronic morphine and cannabinoid addicts and 10 controls with no current or past history of drug abuse; were stimulated by anti-CD3 antibody plus phytoheamagglutinin (PHA). Activation of the NF-κB signaling pathway was examined by analyzing NF-κBp65 in a solid phase sandwich ELISA. IL-17/IL-10 balance was assessed using quantitative ELISA on cultured CD4+ T cells supernatants. We found that, morphine and cannabinoids inhibited NF-κB signaling in activated T cells of addicts, whereas it enhanced activated T cell apoptosis as measured by quantitative in vitro determination of cytoplasmic histone-associated DNA fragmentation following induced cell death. These effects of morphine and cannabinoids T cell suppression were accompanied by elevation of IL-10 level and concomitant reduction in IL-17 secretion from cultured CD4+ T cells. We concluded that Th17/Treg imbalance may be attributed to inhibited NF-κB activity in CD4+ T cells under the effect of morphine and cannabinoids addiction.

Medical consequences of marijuana use: a review of current literature.

With the advent of legalization of marijuana for medicinal and recreational purposes, and the increase use of marijuana, healthcare providers will be increasingly confronted with marijuana users as patients in clinical environments. While there is vast literature regarding the societal and mental health harms associated with marijuana use, there is a paucity of reviews of the potential consequences of marijuana use on physical health or medical conditions. We examine the recent literature on the physical harms associated with illicit and legal marijuana administration. We surveyed the peer-reviewed medical literature from 1998 to 2013 of studies assessing the association of marijuana use and physical diseases. We conclude that healthcare providers should be cognizant that the existing literature suggests that marijuana use can cause physical harm. However, evidence is needed, and further research should be considered, to prove causal associations of marijuana with many physical health conditions.

Cumulative exposure to stimulants and immune function outcomes among HIV-positive and HIV-negative men in the Multicenter AIDS Cohort Study.

We examined associations between stimulant use (methamphetamine and cocaine) and other substances (nicotine, marijuana, alcohol and inhaled nitrites) with immune function biomarkers among HIV-seropositive (HIV +) men taking highly active antiretroviral therapy (ART) and HIV-seronegative (HIV-) men in the Multicenter AIDS Cohort Study. Among HIV + men, cumulative adherence to ART (4.07, 95% confidence interval [CI]: 3.52, 4.71, per 10 years of adherent ART use), and recent cohort enrolment (1.38; 95% CI: 1.24, 1.55) were multiplicatively associated with increase in CD4+/CD8+ ratios. Cumulative use of methamphetamine (0.93; 95% CI: 0.88, 0.98, per 10 use-years), cocaine (0.93; 95% CI: 0.89, 0.96, per 10 use-years) and cumulative medical visits (0.99; 95% CI: 0.98, 0.99, per 10 visit-years), each showed small negative associations with CD4+/CD8+ ratios. Among HIV- men, cumulative medical visits (0.996; 95% CI: 0.993, 0.999), cumulative number of male sexual partners (0.999; 95% CI: 0.998, 0.9998, per 10 partner-years) and cigarette pack-years (1.10; 95% CI: 1.02, 1.18, per 10 pack-years) were associated with CD4+/CD8+ ratios over the same period. ART adherence is associated with a positive immune function independent of stimulant use, underscoring the influence of ART on immune health for HIV+ men who engage in stimulant use.

Allergic hypersensitivity to cannabis in patients with allergy and illicit drug users

Background: Cannabis is the illicit drug most widely used by young people in high-income countries. Allergy symptoms have only occasionally been reported as one of the adverse health effects of cannabis use. Objectives: To study IgE-mediated response to cannabis in drug users, atopic patients, and healthy controls. Methods: Asthmatic patients sensitised to pollen, and all patients sensitised to tobacco, tomato and latex, considered as cross-reacting allergens, were selected from a data base of 21,582 patients. Drug users attending a drug-rehabilitation clinic were also included. Controls were 200 non-atopic blood donors. Specific IgE determination, prick tests and specific challenge with cannabis extracts were performed in patients and controls. Results: Overall, 340 patients, mean age 26.9±10.7 years, were included. Males (61.4%) were the most sensitised to cannabis (p<0.001). All cannabis-sensitised patients were alcohol users. Eighteen (72%) of the patients allergic to tomato were sensitised to cannabis, but a positive specific challenge to cannabis was highest in patients sensitised to tobacco (13/21, 61.9%), (p<0.001). Pollen allergy was not a risk factor for cannabis sensitisation. Prick tests and IgE for cannabis had a good sensitivity (92 and 88.1%, respectively) and specificity (87.1 and 96%) for cannabis sensitisation. Conclusions: Cannabis may be an important allergen in young people. Patients previously sensitised to tobacco or tomato are at risk. Cannabis prick tests and IgE were useful in detecting sensitisation (AU)

[The morphology of the immune system in opiomania, cannabism, and polynarcotism].

The organs of the immune system were morphologically and immunohistochemically studied in chronic opiomania (n = 219), cannabism (n = 22), and polynarcotism (n = 69) after excluding HIV-infected patients. In opiomania, immune disorders were identified in 98.6% of cases. These immune disorders differ according to their stage and characterize by the inversion of the T-helper/T-suppressor index, the reductions in the proliferative activity of lymphocytes and the production of immunoglobulins, atrophy of the thymus and T zones, and, in 37.4% of cases, persistent follicular hyperplasia of B zones with the impaired architectonics of lymphoid follicles. It is a cause of generalized lymphadenopathy and splenomegaly, which are similar to those observed in HIV infection. Infection with hepatitis B and C viruses enhances thymus and T-zone atrophy, but B-tone hyperplasia particularly in the lymph nodes of the hepatic hilum and spleen. In cannabism, the morphological signs of immunodeficiency were revealed only in 13.6% of the dead and there was no inversion of the T-helper/T-suppressor index. In polynarcotism, the involvement of immune organs is most severe and similar to that seen in opiomania.

Combined immunomodulating properties of 3,4-methylenedioxymethamphetamine (MDMA) and cannabis in humans.

AIMS: Cell-mediated immune function and the occurrence of mild infectious diseases was investigated. Participants Polydrug consumers of 3,4-methylenedioxymethamphetamine (MDMA) and cannabis (n = 37) compared to cannabis users only (n = 23) and control group (n = 34). DESIGN: A longitudinal prospective study with three cross-sectional evaluations at time 0 and at 6 months and 1 year was performed. FINDINGS: At baseline, a significant decrease in interleukin (IL)-2 and an increase in anti-inflammatory transforming growth factor (TGF)-beta1, together with a decrease in the number of total lymphocytes, CD4 and natural killer (NK) cells were observed in the MDMA-cannabis group, with intermediate alterations in the cannabis group. Immune alterations observed at baseline were sustained over time. No differences were found between regular and occasional MDMA users. A significantly higher rate of mild infections in regular MDMA-cannabis users compared with occasional MDMA-cannabis users and the remaining groups was observed. CONCLUSIONS: The present data confirm that long-term alterations in immunological homeostasis may result in general health status impairment and subsequent increased susceptibility to infection and immune-related disorders.

Delta 9-Tetrahydrocannabinol regulates Th1/Th2 cytokine balance in activated human T cells.

Human leukocytes express cannabinoid (CB) receptors, suggesting a role for both endogenous ligands and Delta 9-tetrahydrocannabinol (THC) as immune modulators. To evaluate this, human T cells were stimulated with allogeneic dendritic cells (DC) in the presence or absence of THC (0.625-5 microg/ml). THC suppressed T cell proliferation, inhibited the production of interferon-gamma and shifted the balance of T helper 1 (Th1)/T helper 2 (Th2) cytokines. Intracellular cytokine staining demonstrated that THC reduced both the percentage and mean fluorescence intensity of activated T cells capable of producing interferon-gamma, with variable effects on the number of T cells capable of producing interleukin-4. Exposure to THC also decreased steady-state levels of mRNA encoding for Th1 cytokines, while increasing mRNA levels for Th2 cytokines. The CB2 receptor antagonist, SR144528, abrogated the majority of these effects. We conclude that cannabinoids have the potential to regulate the activation and balance of human Th1/Th2 cells by a CB2 receptor-dependent pathway.

Marijuana, receptors and immunomodulation.

THC, the major psychoactive component of marijuana, has been shown both in humans and experimental animals to have immunomodulatory properties. For example, marijuana smokers may show impaired immunological functions, including deficiency of blood leukocyte blastogenesis to mitogens. Detailed studies with mice have shown that animals given THC can show marked immunomodulation, including suppression of antibody formation, deficient cytokine production, etc. However, recent studies have also shown that lymphoid cells evince enhanced production or release or IL1, but suppression of IL2 and interferon production. Such lymphoid cells treated in vitro with THC also show suppressed blastogenesis to antigens and mitogens, suppressed NK activity, etc. In contrast, it has recently been shown that THC can enhance production or release of pro-inflammatory cytokines. This includes release of these cytokines from macrophages, including augmented release of IL1, TNF alpha, and IL6 activity. Susceptibility of mice to infection with opportunistic organisms such as L. pneumophila has been found and this increased susceptibility can be modulated by THC. A toxic shock-like death to Legionella has been induced by THC treatment given one day before and one day after infection. Receptors to THC have been detected in the brain as well as in peripheral tissues, including lymphoid cells. Thus, immunomodulation induced by THC may be related to receptor effects as well as unrelated to such receptors. It is clear that THC and other cannabinoids are excellent tools for studying the mechanisms of immune modulation, especially altered susceptibility to microbial infection.

[Analytical exploration of drug addiction]. / Exploration analytique des toxicomanies.

The natural and synthetic substances most frequently leading to drug addiction are described. They include cannabis, opium and cocaine with their respective derivatives. The authors insist on the problems encountered by analytical chemists when they examine urine samples containing these substances, owing to their metabolic degradation and to interferences between lawful and unlawful drugs. The limitations imposed by these problems to an unambiguous interpretation of the results obtained are defined, but they do not throw any doubt on the value of these investigations.

Marihuana y asma: un caso clínico / Marijuana and asthma: clinic case

Se estudia un paciente fumador de MH, con episodios de asma bronquial desencadenados por la misma, quien declara su drogadicción después de 14 años de consumo, y a quien se investiga. 1.Prick test para ácaros, hongos anemófilos y pólenes, dando resultado positivo para aspergillus fumigatus, mucor y alternaria (el aspergillos suele estar contaminando habitualmente la MH). 2.Se realiza el cultivo para hongos en la vivienda encontrando desarrollo de cladosporium en la misma y de alternancia y cladosporium en el lugar de trabajo. 3.Se busca apergillus en la MH encontrando desarrollo de aspergillus fumigatus y mucor y no existiendo desarrollo de hongos en el tabaco. 4. Se practica test de provocación con ambos, notando un significativo descenso del VEF 1s post inhalación de MH y aparición de sibilancias. Se remarca la importancia del abuso de drogas, a tener en cuenta en el diagnóstico difererencial de los agentes desencadenantes del asma bronquial dado el aumento de consumidores de la misma en los últimos tiempos