Detectability of cannabinoids in the serum samples of cannabis users: Indicators of recent cannabis use? A follow-up study.

Forensic toxicologists are frequently required to predict the time of last cannabis consumption. Several studies suggested the utility of minor cannabinoids as indicators of recent cannabis use. Because several factors influence blood cannabinoid concentrations, the interpretation of serum cannabinoid concentrations remains challenging. To assess the informative value of serum cannabinoid levels in cannabis users (in total N = 117 patients, including 56 patients who stated an exact time of last cannabis use within 24 h before blood sampling), the detectability of cannabinoids, namely, delta-9-tetrahydrocannabinol (delta-9-THC), 11-hydroxy-delta-9-THC, 11-nor-9-carboxy-delta-9-THC, cannabichromene (CBC), cannabidiol (CBD), cannabinol (CBN), cannabidivarin, tetrahydrocannabivarin, cannabigerol (CBG), cannabicyclol, delta-8-THC, tetrahydrocannabinolic acid A, cannabichromenic acid, cannabidiolic acid (CBDA), cannabigerolic acid, cannabicyclolic acid (CBLA), 11-nor-9-carboxy-THCV (THCVCOOH), and 11-nor-CBN-9-COOH, was investigated. Excluding CBDA and CBLA, all investigated cannabinoids were detected in at least one analyzed sample. The interval between cannabis consumption and sample collection (reported by the patients) was not correlated with cannabinoid concentrations. Minor cannabinoids tended to be more easily detected in samples obtained shortly after consumption. However, some samples tested positive for minor cannabinoids despite an interval of several hours or even days between consumption and sampling (according to patients' statements). For instance, CBC, CBG, THCVCOOH, CBD, and CBN in certain cases could be detected more than 24 h after the last consumption of cannabis. Thus, findings of minor cannabinoids should always be interpreted with caution.

Sex differences in the acute effects of oral and vaporized cannabis among healthy adults.

Policy changes have increased access to cannabis for individuals with little or no prior exposure. Few studies have examined sex differences in cannabis effects among individuals with sporadic cannabis use or for nonsmoked routes of cannabis administration. Data from four double-blind, placebo-controlled studies were pooled to compare the acute pharmacodynamic effects of vaporized and oral cannabis in male (n = 27) and female (n = 23) participants who used cannabis infrequently (no use ≥30 days prior to randomization). Analyses compared peak change-from-baseline scores between male and female participants for subjective drug effects, cognitive/psychomotor performance, cardiovascular effects, and blood concentrations of Δ9-tetrahydrocannabinol (THC) and its primary metabolites (11-OH-THC, THC-COOH) after exposure to placebo cannabis or cannabis containing low-dose (5 or 10 mg) or high-dose THC (20 or 25 mg). Overall, cannabis elicited dose-orderly increases in subjective effects, impairment of cognitive/psychomotor performance, heart rate, and blood cannabinoid concentrations. Females exhibited greater peak blood 11-OH-THC concentrations and reported greater peak subjective ratings of "drug effect" that remained when controlling for body weight. When controlling for both body weight and peak blood cannabinoid concentrations, ratings of "anxious/nervous," "heart racing," and "restless" were significantly higher for females than males. Although additional research is needed to elucidate sex differences in responses to cannabis at a wider range of THC doses, other routes of administration, and products with diverse chemical composition, the current data indicate that public health messaging and clinical decision making around the use of cannabinoids should recommend lower starting doses for females and warnings about acute anxiogenic reactions.

The association between cannabis use and testicular function in men: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between cannabis use and testicular function (as assessed through semen quality and serum hormone levels) in different populations. EVIDENCE REVIEW: Systematic review and meta-analysis of population-based retrospective cohort studies. PRISMA guidelines were used for abstracting data and assessing data quality and validity. Data were pooled using a fixed-effects or random-effects model depending on the heterogeneity of studies included. Pooled risk ratio (RR) of having any sperm abnormality and testosterone, FSH, and LH standardized mean differences among male cannabis users and non-users, and meta-regression analysis according to age and year of publication. RESULTS: Nine studies were evaluated which included 4014 men with semen data and 4787 with hormonal data. Overall among 1158 cannabis users, 44.9% had impaired semen parameters, compared with 24.5% of the 2856 non-users. The relative risk among cannabis users for any abnormal semen parameter was 1.159 (95% CI: 0.840; 1.599, P = 0.369). The standardized mean difference between user and non-user testosterone levels was -0.139 (95% CI: -0.413; 0.134, P = 0.318). For FSH, the standardized mean difference estimate was -0.142 (95% CI: -0.243; -0.0425, P = 0.005), while for LH the standardized mean difference estimate was -0.318 (95% CI: -0.810-0.175; P = 0.206). CONCLUSIONS: The current evidence does not suggest clinically significant associations between cannabis use and testicular function. However, we cannot exclude an effect of cannabis because of the limited and heterogeneous studies. Additionally, well-designed studies will be needed to define the association between cannabis use and the male reproductive system.

Lifetime marijuana use in relation to cadmium body burden of US adults: results from the national health and nutrition examination surveys, 2009-2016.

OBJECTIVES: Low-level cadmium exposure has been linked to chronic diseases, but the importance of marijuana use as a source of cadmium remains unknown. We aimed to determine the association of marijuana use with blood cadmium (BCd) and urinary cadmium (UCd) levels. METHODS: We abstracted data from the National Health and Nutrition Examination Surveys, 2009-2016. We modeled lifetime marijuana exposure accounting for both duration and frequency of exposure. We used adjusted ratio of geometric means (ARM) and 95% confidence intervals (95% CIs) to compare outcomes among groups of marijuana exposure, relative to never users. The UCd level was adjusted for creatinine excretion. RESULTS: We included 163,250 adults (mean age, 38.7 years; 50% women). The ARM of BCd was 1.28 (95% CI = 1.04, 1.57), 1.40 (95% CI = 1.11, 1.76), and 1.77 (95% CI = 1.51, 2.09) in current users with <2 uses per week, 2-3 uses per week, and ≥4 uses per week, respectively. Marijuana use for ≥15 years was associated with both higher cadmium burden in adults with <2 uses per week (ARM of 1.30 (95% CI = 1.04-1.62) for BCd and 1.48 (95% CI: 1.05, 2.09) for UCd or ≥4 uses per week (ARM of 1.69 (95% CI = 1.40, 2.05) for BCd and 1.38 (95% CI = 1.11, 1.72) for UCd. In former users, marijuana use was significantly associated with higher UCd levels in those with ≥15 years of use [ARM of 1.39 (95% CI = 1.14, 1.69) for those with <2 uses/week and 1.51 (95% CI = 1.19, 1.92) for those with ≥4 uses/week]. CONCLUSIONS: The BCd level was higher in both current and former marijuana users than in never users. Marijuana use was also associated with higher UCd levels after a long-term use.

Cannabinoid use in psychotic patients impacts inflammatory levels and their association with psychosis severity.

Inflammatory abnormalities are well-documented in individuals with chronic psychotic disorders. Particular attention has focused on interleukin-6 (IL-6) and its correlation with psychotic symptom severity. Cannabis use is associated with an increased risk of psychosis and also has immunomodulating properties. It has been hypothesized that inflammatory disturbances are a common underlying pathology between cannabis use and psychosis. We measured inflammatory markers in individuals admitted to a psychiatric unit with acute psychosis who had toxicology positive for natural and/or synthetic cannabinoids (n = 59) compared to patients with negative cannabinoid toxicology (n = 60). Psychosis severity was assessed using the Positive and Negative Syndrome Scale (PANSS). While PANSS scores were similar between groups, cannabinoid-positive participants were more likely to receive pro re nata (PRN or as-needed) medications for agitation in the psychiatric emergency room, particularly synthetic cannabinoid-positive participants. In unadjusted models, cannabinoid-positive participants had lower interferon-γ (IFN-γ) levels (p = 0.046), but this finding was not significant after adjusting for covariates and multiple comparisons. Among cannabinoid-positive participants, IL-6 levels negatively correlated with PANSS total score (p = 0.040), as well as positive (p = 0.035) and negative (p = 0.024) subscales. Results suggest inflammatory alterations among psychotic individuals with comorbid cannabinoid use.

Cannabis use influence on peripheral brain-derived neurotrophic factor levels in antipsychotic-naïve first-episode psychosis.

The objective of this study is to determine whether cannabis influences BDNF levels in patients with psychosis (FEP) and healthy volunteers (HV) to help understand the role of BDNF in psychosis. We assessed the association between BDNF and cannabis in a cohort of FEP antipsychotic-naïve patients and HV, whilst controlling for other potential confounding factors. 70 FEP drug-naive patients and 57 HV were recruited. A sociodemographic variable collection, structured clinical interview, weight and height measurement, substance use determination, and blood collection to determine BDNF levels by ELISA analysis were done. In FEP patients, cannabis use was associated with BDNF levels (high cannabis use was associated with lower BDNF levels). Moreover, cannabis use was statistically significantly associated with age (high use of cannabis was associated with younger age). In HV, no relationship between cannabis use and BDNF levels was observed. Otherwise, cannabis use was significantly associated with tobacco use, so that high cannabis users were also high tobacco users. This study showed a different association between cannabis use and BDNF levels in FEP patients compared with HV, particularly, with high doses of cannabis. These findings may help understand the deleterious effects of cannabis in some vulnerable individuals, as well as discrepancies in the literature.

Chronic marijuana use moderates the correlations of serum cholesterol with systemic mitochondrial function and fluid cognition.

Activating type 1 cannabinoid (CB1) receptor decreases the particle size of high-density lipoprotein (HDL) and inhibits reverse cholesterol transport (RCT). This study examined whether marijuana (MJ) use is associated with changes of RCT, and how the latter is associated with mitochondrial function and fluid cognition. We recruited 19 chronic MJ users and 20 nonusers with matched age, BMI, sex, ethnicity, and education. We measured their fluid cognition, mitochondrial function (basal and max respiration, ATP production) in peripheral blood mononuclear cells, cholesterol content in serum lipoprotein fractions, enterolactone/creatinine ratio in urine as a marker for dietary polyphenol intake, and lipase activity in serum. We found that higher percentage of large HDL cholesterol (HDL-C) correlated positively, while that of small HDL-C correlated inversely, with mitochondrial function among MJ users, but correlations of the opposite directions were found among nonusers. The concentrations of large and intermediate HDL-C correlated positively with mitochondrial function and fluid cognition among MJ users, but not among nonusers. Both percentage and concentration of large HDL-C correlated positively, while those of small HDL-C correlated inversely, with amounts of daily and lifetime MJ use. In all participants, higher urinary enterolactone/creatinine ratio and lower serum lipase activity were associated with higher large HDL-C/small HDL-C ratio, implying greater RCT. This study suggests that high MJ use may compromise RCT, which is strongly associated with mitochondrial function and fluid cognition among MJ users.

Chronic cannabis use and circulating biomarkers of neural health, stress, and inflammation in physically active individuals.

Previous research has associated cannabis use with altered circulating neurotrophins and biomarkers of immune health, but these relationships have yet to be fully explored in physically active individuals. The specific aim of this study was to explore the relationships between biomarkers of neural health: nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), immune health: interleukin 6 (IL-6), C-reactive protein (CRP), and cortisol, as well as the presence of depression, in physically active cannabis users (CU) and nonusers (NU). Male and female participants (N = 30; CU, n = 15, NU, n = 15) provided intravenous blood samples and underwent assessment of body composition, maximal oxygen consumption, and depression (Beck Depression Inventory-II (BDI-II)). Samples were analyzed for concentrations of NGF, BDNF, IL-6, CRP, and cortisol using ELISAs. CU and NU were compared using an unpaired t test. Pearson's correlation and multiple linear regression were used to evaluate relationships among variables. There were no significant differences in body size or composition, maximal oxygen consumption, total BDI-II Score, concentrations of NGF, IL-6, CRP, or cortisol between groups. BDNF was significantly lower in CU compared with NU (p = 0.02), with a significant negative relationship between BDNF and CRP (p = 0.02). Mean concentrations of CRP placed CU at higher risk for cardiovascular disease compared with NU. Total BDI-II score negatively correlated with BDNF (p = 0.02) and positively correlated with CRP (p = 0.02). Novelty Plasma BDNF was significantly lower in physically active cannabis users compared with NU. CU were classified at moderate risk for cardiovascular disease based on average circulating CRP compared with low risk for NU.

Lifetime marijuana use in relation to insulin resistance in lean, overweight, and obese US adults.

BACKGROUND: Obese individuals are more likely to show insulin resistance (IR). However, limited population studies on marijuana use with markers of IR have yielded mixed results. The aim of this study was to examine the association of marijuana use with IR in US adults with different body mass index (BMI) status. METHODS: Data from the 2009 to 2016 National Health and Nutrition Examination Survey (NHANES) were abstracted. Minimal lifetime marijuana use was estimated using the duration of regular exposure and frequency of use. The association of marijuana use with both fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) was determined in lean, overweight, and obese individuals separately using generalized linear models. Interview weight years of data were used to account for the unequal probability of sampling and non-response. RESULTS: Of all 129 509 adults aged 18 to 59 years, 50.3% were women. In current obese marijuana consumers, mean FINS in those with less than four uses per month was 52% (95% confidence interval [CI] 19%-71%) lower than in never users. In former obese consumers with eight or more uses per month and who stopped marijuana use <12 months ago, mean FINS was 47% (95% CI 18%-66%) lower than in never users. Mean FINS in those who quit marijuana 12 to 119 and 120 months and more prior the survey was 36% (95% CI 7%-57%) and 36% (95% CI 10%-54%) lower, respectively. CONCLUSIONS: Marijuana use is associated with lower FINS and HOMA-IR in obese but not non-obese adults, even at low frequency of less than four uses per month. Former marijuana consumers with high lifetime use had significantly lower FINS levels that persisted, independent of the duration of time since last use.

Strengths and limitations of two cannabis-impaired driving detection methods: a review of the literature.

Background: Recent cannabis use is associated with an approximate two-fold increase in automobile crash risk, but detecting cannabis-impaired driving remains a challenge.Objectives and Methods: In this perspective, the pros and cons of two types of assessments arising from those used to detect alcohol-impaired driving are discussed in the context of cannabis-impaired driving.Results: Some laws rely on tests to detect whether blood or breath levels exceed a legally defined (per se) threshold. These laws rely on clear and consistent relationships across individuals between detectable drug concentrations and the amount consumed, crash risk, or degree of driver impairment. However, unlike alcohol, there is poor correspondence between detected levels of the primary active constituent of cannabis or its metabolites and the amount consumed or its behavioral effects. Field sobriety tests assess impairment on functional tests calibrated to reflect actual driving-impairment and validated to predict traffic safety risk. However, functional tests for cannabis-impaired driving have not been developed or validated, and the degree of impairment resulting from recent cannabis use is difficult to distinguish from other conditions such as advancing age or use of certain medications.Conclusions: Although standard field sobriety tests have advantages over per se tests for cannabis-impaired driving, limitations of both leave cannabis users and law enforcement officials little guidance in assessing an individual's driving fitness after recent cannabis use. General strategies for detecting and preventing impaired driving regardless of the cause would be preferable to establishing specific methods for every situation or substance that could impair driving.

Total and Differential White Blood Cell Counts, Cocaine, and Marijuana Use in Patients With Schizophrenia.

Schizophrenia is associated with blood inflammatory marker abnormalities. Illicit drug use, which is common in schizophrenia, may modulate inflammatory marker levels. We examined effects of marijuana and cocaine use on white blood cell (WBC) counts in acutely ill, hospitalized patients with schizophrenia using a within-subjects and between-groups design. Mean total and differential WBC counts were first compared in acutely ill patients with schizophrenia for hospitalizations with and without either marijuana (n = 18) or cocaine (n = 24) use. Mean total and differential WBC counts were then compared between patients with schizophrenia with either marijuana or cocaine use and patients with a negative urine drug screen (UDS; n = 43). Patients with schizophrenia had significantly higher total WBC, lymphocytes, and monocytes during hospitalizations with (vs. without) cocaine use. Patients with cocaine use also had significantly higher monocytes and eosinophils than those with a negative UDS. Our findings suggest that substance use, particularly of cocaine, may modulate inflammatory marker levels in acutely ill, hospitalized patients with schizophrenia.

Cannabis use as a risk factor for causing motor vehicle crashes: a prospective study.

AIM: We conducted a responsibility analysis to determine whether drivers injured in motor vehicle collisions who test positive for Δ-9-tetrahydrocannabinol (THC) or other drugs are more likely to have contributed to the crash than those who test negative. DESIGN: Prospective case-control study. SETTING: Trauma centres in British Columbia, Canada. PARTICIPANTS: Injured drivers who required blood tests for clinical purposes following a motor vehicle collision. MEASUREMENTS: Excess whole blood remaining after clinical use was obtained and broad-spectrum toxicology testing performed. The analysis quantified alcohol and THC and gave semiquantitative levels of other impairing drugs and medications. Police crash reports were analysed to determine which drivers contributed to the crash (responsible) and which were 'innocently involved' (non-responsible). We used unconditional logistic regression to determine the likelihood (odds ratio: OR) of crash responsibility in drivers with 0 < THC < 2 ng/ml, 2 ng/ml ≤ THC < 5 ng/ml and THC ≥ 5 ng/ml (all versus THC = 0 ng/ml). Risk estimates were adjusted for age, sex and presence of other impairing substances. FINDINGS: We obtained toxicology results on 3005 injured drivers and police reports on 2318. Alcohol was detected in 14.4% of drivers, THC in 8.3%, other drugs in 8.9% and sedating medications in 19.8%. There was no increased risk of crash responsibility in drivers with THC < 2 ng/ml or 2 ≤ THC < 5 ng/ml. In drivers with THC ≥ 5 ng/ml, the adjusted OR was 1.74 [95% confidence interval (CI) = 0.59-6.36; P = 0.35]. There was significantly increased risk of crash responsibility in drivers with blood alcohol concentration (BAC) ≥ 0.08% (OR = 6.00;95% CI = 3.87-9.75; P < 0.01), other recreational drugs detected (OR = 1.82;95% CI = 1.21-2.80; P < 0.01) or sedating medications detected (OR = 1.45; 95%CI = 1.11-1.91; P < 0.01). CONCLUSIONS: In this sample of non-fatally injured motor vehicle drivers in British Columbia, Canada, there was no evidence of increased crash risk in drivers with Δ-9-tetrahydrocannabinol < 5 ng/ml and a statistically non-significant increased risk of crash responsibility (odds ratio = 1.74) in drivers with Δ-9-tetrahydrocannabinol ≥ 5 ng/ml.

Is marijuana use associated with lower inflammation? Results from waves III and IV of the national longitudinal study of adolescent to adult health.

BACKGROUND: Some research suggests that marijuana use facilitates an anti-inflammatory response, yet the relationship between marijuana use and inflammation, as measured by C-reactive protein (CRP), remains poorly understood. The present study examined the association between recency of marijuana use and serum C-reactive protein levels in a nationally representative sample of adults. METHODS: Data from Waves III and IV (N = 13,166) of the National Longitudinal Study of Adolescent to Adult Health was utilized. Past 30 day marijuana use was assessed in Waves III and IV, and past year marijuana use was also assessed at Wave IV. CRP was dichotomized with a cutpoint of 3 mg/L. Logistic regression analyses examined the association between marijuana use and CRP levels at Wave IV. RESULTS: Past 30 day marijuana use was reported by 23.5% and 17.7% of participants at Wave III and Wave IV respectively, and 23.6% of participants reported past year marijuana use during Wave IV. Marijuana use was associated with lower CRP levels in bivariate analyses. However, these associations attenuated after adjusting for sociodemographic and health-related covariates. CONCLUSIONS: Though marijuana and lower CRP levels were initially associated, the effect of marijuana use on CRP was later explained by gender, BMI, and anti-inflammatory medication use. This suggests that marijuana use does not confer an anti-inflammatory effect and recency of use is not relevant. Given expanding marijuana use legislation and discourse surrounding the consequences of marijuana for health, continued research is needed to elucidate the effect of marijuana on inflammation and subsequent risk of chronic disease.

Confirmed marijuana use and lymphocyte count in black people living with HIV.

BACKGROUND: Marijuana is a commonly used recreational substance with purported analgesic and mood enhancing properties. Many people living with HIV identify marijuana as a palliative substance. However, through its main psychoactive component, tetrahydrocannabinol (THC), is known to influence the immune system. The effects of marijuana use in people with HIV are still controversial, with very scant literature in Black adults. METHODS: The current study determined the differences in the lymphocyte count, specifically the number cluster differentiation 4 and 8 (CD4+ and CD8+), among patients who urine drug tested negative for THC (n = 70) and those who tested positive for THC (n = 25). The sample included 95 Black people living with HIV, 51% female, with a mean age of 46 ± 11 years. Participants provided a urine sample for substance use testing and a trained researcher extracted clinical data from clinical charts on the day of appointment. RESULTS: After adjusting for demographic and HIV-related covariates, THC-positive patients had significantly higher CD4+ and CD8+ counts than their THC-negative counterparts. CONCLUSION: These results extend previous HIV-related immunity findings in an underrepresented group, and suggest that THC use does not reduce immune function as measured by CD count. Further research is warranted on the overall effects of THC on immune function in HIV positive patients.

Alcohol and marijuana use among young injured drivers in Arizona, 2008-2014.

OBJECTIVE: We examined alcohol and marijuana use among injured drivers aged 16-20 years evaluated at Arizona level 1 trauma centers during 2008-2014. METHODS: Using data from the Arizona State Trauma Registry, we conducted a descriptive analysis of blood alcohol concentration (BAC) and qualitative test results (positive or negative) for delta-9-tetrahydrocannabinol (THC) by year of age, sex, race, ethnicity, injury severity, seat belt use, motorcycle helmet use, and type of vehicle driven. To explore compliance with Arizona's motorcycle helmet law requiring helmet use for riders <18 years old, we examined helmet use by age. RESULTS: Data on 5,069 injured young drivers were analyzed; the annual number of injured drivers declined by 41% during the 7-year study period. Among the 76% (n = 3,849) of drivers with BAC results, 19% tested positive, indicating that at least 15% of all drivers had positive BACs. Eighty-two percent of the BAC-positive drivers had BACs ≥0.08 g/dL, the illegal threshold for drivers aged ≥21 years. Among the 49% (n = 2,476) of drivers with THC results, 30% tested positive, indicating that at least 14% of all drivers were THC-positive. American Indians and blacks had the highest proportion of THC-tested drivers with positive THC results (38%). In addition, 28% of tested American Indians had positive results for both substances, more than twice the proportion seen in all other race or ethnic groups. Crude prevalence ratios suggested that drivers who tested positive for alcohol or THC were less likely than those who tested negative to wear a helmet or seat belt, further increasing their injury risk. Helmet use among motorcyclists was lower among 16- and 17-year-old riders compared to 18- to 20-year-olds, despite Arizona's motorcycle helmet law requiring riders aged <18 years to wear a helmet. CONCLUSIONS: About 1 in 4 injured drivers aged 16-20 years tested positive for alcohol, THC, or both substances. Most drivers with positive BACs were legally intoxicated (BAC ≥0.08 g/dL). All substance-using young drivers in this study were candidates for substance abuse screening and possible referral to treatment. Broader enforcement of existing laws targeting underage access to alcohol and alcohol-impaired driving could further reduce injuries among young Arizona drivers. To further reduce crash-related injuries and fatalities among all road users, the state could consider implementing a primary enforcement seat belt law and a universal motorcycle helmet law.

Associations Between Cannabis Use and Cardiometabolic Risk Factors: A Longitudinal Study of Men.

OBJECTIVE: This study tested longitudinal associations between cannabis use and cardiometabolic risk factors that underlie the development of cardiovascular diseases. METHODS: Participants were men from the youngest cohort of the Pittsburgh Youth Study who were followed prospectively from approximately age 7 to 32 years (N = 253). Frequency of cannabis use was assessed yearly from approximately ages 12 to 20 years and again at approximately ages 26, 29, and 32 years. The following cardiometabolic risk factors were assessed during a laboratory visit at approximately age 32 years: body mass index (BMI), waist-hip ratio, high- and low-density lipoprotein cholesterol, triglycerides, fasting glucose, insulin resistance, blood pressure, interleukin 6, and C-reactive protein. RESULTS: Greater cannabis exposure was associated with relatively lower BMI (ß = -0.31, p < .001), smaller waist-hip ratio (ß = -0.23, p = .002), better high- (ß = 0.14, p = .036) and low-density lipoprotein cholesterol (ß = -0.15, p = .026), lower triglycerides (ß = -0.17, p = .009), lower fasting glucose (ß = -0.15, p < .001) and insulin resistance (ß = -0.21, p = .003), lower systolic (ß = -0.22, p < .001) and diastolic blood pressure (ß = -0.15, p = .028), and fewer metabolic syndrome criteria (ß = -0.27, p < .001). With exception of BMI, cannabis users' mean levels on cardiometabolic risk factors were generally below clinical cutoffs for high risk. Most associations between cannabis use and cardiometabolic risk factors remained after adjusting for tobacco use, childhood socioeconomic status, and childhood health. However, after adjusting for adult BMI, these associations were no longer apparent, and mediation tests suggested that cannabis users' relatively lower BMI might explain their lower levels of risk on other cardiometabolic risk factors. CONCLUSIONS: Cannabis use is associated with lower BMI, and lower BMI is related to lower levels of risk on other cardiometabolic risk factors.

8ß-OH-THC and 8ß,11-diOH-THC-minor metabolites with major informative value?

The ∆9-tetrahydrocannabinol (THC) metabolites 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC are mentioned in the literature as potential blood markers of recent cannabis use. However, the formation of these metabolites in in vivo detectable concentrations has been described controversially. Therefore, the aim of this study was to verify the in vivo metabolism of 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC in order to evaluate their potential as blood markers of recent cannabis use. First, we developed and validated a solid-phase-extraction method coupled with gas chromatography-mass spectrometry in order to enable the selective and very sensitive determination of 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC. The application of this method in the analysis of 70 authentic plasma samples of cannabis users revealed positive results for both analytes. We detected 8ß-hydroxy-THC in three and 8ß,11-dihydroxy-THC in 37 out of the 70 analyzed samples. For 8ß-hydroxy-THC, all of the three positive results were below the limit of quantification (LOQ; 0.3 ng/mL) but above the limit of detection (LOD; 0.2 ng/mL). For 8ß,11-dihydroxy-THC, only two positive results were below the LOQ (0.4 ng/mL) but above the LOD (0.3 ng/mL); the remaining 35 were quantified. Hence, we were able to prove the in vivo metabolism from THC to both 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC in detectable concentrations. The quantitative comparison of 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC with the main cannabinoids THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC revealed no further informative value for 8ß-hydroxy-THC regarding the last time of cannabis consumption. However, the detectability from 8ß,11-dihydroxy-THC compared to 11-hydroxy-THC suggests a shorter detection time for 8ß,11-dihydroxy-THC and thereby a promising application of this metabolite as a blood marker of recent cannabis use.

Marijuana use is associated with hypersensitivity to multiple allergens in US adults.

BACKGROUND: The recent legalization of marijuana use for both medical and recreational purposes in several states of the United Sates is expected to further increase the already high prevalence of marijuana use. Although allergic reactions are uncommon, the potential of marijuana use and cultivation to cause allergy should be considered. We aimed to investigate whether marijuana use is associated with the prevalence of sensitization to specific allergens. METHODS: A total of 2671 adults (aged 20-59 years) who participated in the 2005-2006 National Health and Nutrition Examination Survey were included. Participants completed a questionnaire on marijuana use and underwent sensitization tests to 19 specific allergens. Those who reported marijuana use for at least 1 day in the past 30 days were considered marijuana users. RESULTS: No difference was found in the history of allergy between marijuana users and non-users. Compared with marijuana non-users as a reference group, the adjusted odds ratio (AOR) of sensitization to a specific allergen among marijuana users was significantly greater for antibodies against the following: Alternaria alternata (AOR=1.67; 95% confidence interval (CI), 1.04-2.70), D. farinae (AOR=1.68; 95% CI, 1.27-2.22), D. pteronyssin (AOR=1.65; 95% CI, 1.32-2.06), ragweed (AOR=1.84; 95% CI, 1.30-2.59), rye grass (AOR=1.49; 95% CI, 1.12-1.97), Bermuda grass (AOR=1.55; 95% CI, 1.03-2.33), oak (AOR=1.76; 95% CI, 1.14-2.70), birch (AOR=2.09; 95% CI, 1.23-3.55), peanut (AOR=1.91; 95% CI, 1.25-2.92), and cat dander (AOR=1.51; 95% CI=1.13-2.03). CONCLUSIONS: We provide preliminary findings to suggest that marijuana use is associated with sensitization to specific allergens, including molds, dust mites, plants, and cat dander.

Effect of Marijuana Use on Thyroid Function and Autoimmunity.

BACKGROUND: Marijuana is legalized for medical use in 24 states and for recreational use in 5. However, effects of marijuana use on thyroid function and autoimmunity are unknown. METHODS: We performed a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2012 to assess the effects of marijuana on thyroid function and autoimmunity in users. We included 5280 adults ages 18 to 69 years, who responded to questions related to marijuana use and had laboratory results related to thyroid parameters. Subjects were categorized as nonusers (never used), past users (used prior to 30 days ago), and recent users (used within last 30 days). Using NHANES normative cut offs for thyroid parameters, we compared recent users with nonusers and past users and calculated the odds ratios for the relative rate of clinically significant thyroid dysfunction in those groups. Multivariate logistic regression was then performed to control for confounders. RESULTS: Fifty-four percent of subjects reported lifetime cannabis use, with 15% using it recently. Univariate regression analysis showed that recent marijuana users had significantly lower frequency of elevated thyrotropin (TSH) and positive anti-thyroperoxidase antibody (TPOAb) versus nonusers/past users. After controlling for confounders, recent marijuana use remained an independent predictor for TSH <5.6 µIU/mL (odds ratio of 0.344 with 95% CI of 0.127-0.928; p = 0.04) but not for negative TPOAb. CONCLUSION: Recent marijuana use was not associated with thyroid dysfunction but was significantly associated with lower levels of TSH.