Acute cannabidiol treatment enhances social interaction in adult male mice.

Cannabidiol (CBD) is a non-intoxicating phytochemical from Cannabis sativa that is increasingly used to manage pain. The potential for CBD to ameliorate dimensional behavior symptoms occurring in multiple psychiatric disorders was suggested, including social interaction impairments. To test this hypothesis, adult male BTBRT+Itpr3tf/J (BTBR) mice, a model of idiopathic autism exhibiting social preference deficits and restrictive repetitive behaviors, were acutely treated with vehicle or 0.1, 1, or 10 mg/kg CBD. Social interaction preference was assessed 50 min after treatment, followed by social novelty preference at 60 min, marble burying at 75 min and social dominance at 120 min. CBD (10 mg/kg) enhanced BTBR social interaction but not social novelty preference, marble burying or dominance, with serum levels = 29 ± 11 ng/mg at 3 h post-injection. Next, acute 10 mg/kg CBD was compared to vehicle treatment in male serotonin transporter (SERT) knock-out mice, since SERT deficiency is an autism risk factor, and in their wildtype background strain controls C57BL/6J mice. CBD treatment generally enhanced social interaction preference and attenuated social novelty preference, yet neither marble burying nor dominance was affected. These findings show acute treatment with as little as 10 mg/kg purified CBD can enhance social interaction preference in male mice that are otherwise socially deficient.

Acetaminophen Use for Fever in Children Associated with Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restrictive behavior, interests, and activities. Our previous case-control study showed that use of acetaminophen at age 12-18 months is associated with increased likelihood for ASD (OR 8.37, 95% CI 2.08-33.7). In this study, we again show that acetaminophen use is associated with ASD (p = 0.013). Because these children are older than in our first study, the association is reversed; fewer children with ASD vs. non-ASD children use acetaminophen as a "first choice" compared to "never use" (OR 0.165, 95% CI 0.045, 0.599). We found significantly more children with ASD vs. non- ASD children change to the use of ibuprofen when acetaminophen is not effective at reducing fever (p = 0.033) and theorize this change in use is due to endocannabinoid system dysfunction. We also found that children with ASD vs. non-ASD children are significantly more likely to show an increase in sociability when they have a fever (p = 0.037) and theorize that this increase is due to anandamide activation of the endocannabinoid system in ASD children with low endocannabinoid tone from early acetaminophen use. In light of this we recommend that acetaminophen use be reviewed for safety in children.

Acetaminophen, pesticide, and diethylhexyl phthalate metabolites, anandamide, and fatty acids in deciduous molars: potential biomarkers of perinatal exposure.

The developing fetus is particularly vulnerable to adverse effects from pharmaceutical and exogenous chemical exposure. Deciduous teeth primarily form over specific periods from the second trimester in utero through the months after birth. We hypothesized that organic chemicals or their metabolites circulating in the bloodstream may sorb into forming dental tissues and remain stored in the tooth thereafter. Our aims were to devise analytical and preparation methods for potentially toxic or beneficial organic chemicals or metabolites in deciduous teeth and to estimate their detection frequencies. The analgesic acetaminophen was stored at greater concentration in a child's second molar than a first molar, consistent with intake, suggesting that acetaminophen concentration in molars may be a biomarker of acetaminophen exposure during molar formation. Chemicals detected by liquid chromatography/tandem mass spectrometry in molars of 21 typically developing children include the endocannabinoid anandamide (86% of children), acetaminophen (43%), and specific metabolites mono-2-ethylhexyl phthalate (MEHP, of plasticizer di-2-ethylhexyl phthalate, 29%), 3,5,6-trichloro-2-pyridinol (TCPy, of organophosphate (OP) insecticide chlorpyrifos, 10%), and 2-isopropyl-6-methyl-4-pyrimidinol (IMPy, of OP insecticide diazinon, 10%). None of these chemicals has previously been detected in human teeth. Molars from the two oldest subjects contained the largest concentrations of MEHP, TCPy, and IMPy. Potentially protective fatty acids detected by gas chromatography/mass spectrometry after derivatization include docosahexaenoic (19%), arachidonic (100%), and linoleic (100%). Validation studies are necessary to verify that each detected chemical in molars provides a biomarker of perinatal exposure.

Acetaminophen differentially enhances social behavior and cortical cannabinoid levels in inbred mice.

Supratherapeutic doses of the analgesic acetaminophen (paracetomol) are reported to promote social behavior in Swiss mice. However, we hypothesized that it might not promote sociability in other strains due to cannabinoid CB(1) receptor-mediated inhibition of serotonin (5-HT) transmission in the frontal cortex. We examined the effects of acetaminophen on social and repetitive behaviors in comparison to a cannabinoid agonist, WIN 55,212-2, in two strains of socially-deficient mice, BTBR and 129S1/SvImJ (129S). Acetaminophen (100mg/kg) enhanced social interactions in BTBR, and social novelty preference and marble burying in 129S at serum levels of ≥70 ng/ml. Following acetaminophen injection or sociability testing, anandamide (AEA) increased in BTBR frontal cortex, while behavior testing increased 2-arachidonyl glycerol (2-AG) levels in 129S frontal cortex. In contrast, WIN 55,212-2 (0.1mg/kg) did not enhance sociability. Further, we expected CB(1)-deficient (+/-) mice to be less social than wild-type, but instead found similar sociability. Given strain differences in endocannabinoid response to acetaminophen, we compared cortical CB(1) and 5-HT(1A) receptor density and function relative to sociable C57BL/6 mice. CB(1) receptor saturation binding (Bmax=958±117 fmol/mg protein), and affinity for [(3)H] CP55,940 (K(D)=3±0.8 nM) was similar in frontal cortex among strains. CP55,940-stimulated [(35)S] GTPγS binding in cingulate cortex was 136±12, 156±22, and 75±9% above basal in BTBR, 129S and C57BL/6 mice. The acetaminophen metabolite para-aminophenol (1 µM) failed to stimulate [(35)S] GTPγS binding. Hence, it appears that other indirect actions of acetaminophen, including 5-HT receptor agonism, may underlie its sociability promoting properties outweighing any CB(1) mediated suppression by locally-elevated endocannabinoids in these mice.

The severity of oral/facial problems treated in Iraq March 2008 to February 2009.

BACKGROUND: The objective of this study was to describe the severity of oral/facial problems occurring in Navy and Marine Corps personnel deployed to Iraq. METHODS: Data documented by Navy Dental Officers deployed to Iraq were used to determine the number and type of oral/facial problems treated and to determine the percentages of severe, moderately severe, and pain/loss of function oral/facial problems treated in Iraq from March 2008 through February 2009. RESULTS: During the year of data collection, a total of 13,933 dental visits were documented for Navy and Marine Corps personnel. Of these, 1,641 were encounters to treat an oral/facial problem in Navy and Marine Corps personnel. In all, 37 (2.2%) of the 1,641 encounters for oral/facial problems were considered severe, 266 (16.2%) moderately severe, and 1,338 (81.5%) were for pain/loss of function. CONCLUSIONS: Although the majority of military personnel with oral/facial problems experience mild to moderate pain or loss of dental function, approximately 20% are of sufficient severity to cause the warfighter to experience a limitation of their operational capability.

Does thimerosal or other mercury exposure increase the risk for autism? A review of current literature.

This report reviews current literature regarding the association of the pharmaceutical preservative thimerosal and other mercury exposures with the risk for autism. The evidence presented here does not support a causal association between autism and mercury exposure from the preservative thimerosal. The risk for autism from other mercury exposures such as from dental amalgam restorations or environmental mercury release into the atmosphere is ambiguous. Since mercury is a known neurotoxin, more research should be done to ensure that mercury exposure from any source does not contribute to autism.

Can autism be triggered by acetaminophen activation of the endocannabinoid system?

Acetaminophen use in children has been associated with increased autism risk. Recent evidence suggests that acetaminophen's analgesic actions result from activation of the endocannabinoid system, and activation of this system can have neuromodulatory consequences during development. This investigation was performed to determine if there is evidence to support the hypothesis that acetaminophen use can trigger autism by activation of the endocannabinoid system.

Comparison of pulmonary function in immigrant vs US-born Asian Indians.

OBJECTIVE: This study investigated whether there is a difference in pulmonary function between healthy adult US-born Asian Indians and immigrant Asian Indians attributable to country of birth, environmental, and socioeconomic factors. DESIGN: FEV(1), FVC, and forced mid-expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) were measured in India-born and US-born subjects residing in the Chicago metropolitan area. Hollingshead Index of Social Position was used to evaluate socioeconomic factors. RESULTS: There were 262 India-born (61.8% male), and 200 US-born (50% male) subjects who were healthy lifelong nonsmokers; their age range was 16 to 36 years. US-born Asian Indian men and women were taller and had higher pulmonary function values for height and age compared with immigrant Asian Indian men and women. The differences were most pronounced in women: about 7% for FVC, 9% for FEV(1), and 17% for FEF(25-75). Immigrant and US-born subjects did not differ in socioeconomic position. CONCLUSION: We conclude that US-born Asian Indian men and women have higher pulmonary function values for age and height compared with immigrant Asian Indian men and women. This probably reflects the effect of differing environmental conditions, which cause year-of-birth trends in lung volumes.

Similarities in features of autism and asthma and a possible link to acetaminophen use.

Autism and autism spectrum disorders are enigmatic conditions that have their origins in the interaction of genes and environmental factors. In this hypothesis, genes statistically associated with autism are emphasized to be important in inflammation and in innate immune pathways, including pathways for susceptibility to asthma. The role of acetaminophen (paracetamol) in an increased risk for asthma is described and a possible similar link to an increased risk for autism is suggested.

Comparison of chlorine and chloramine in the release of mercury from dental amalgam.

The purpose of this project was to compare the ability of chlorine (HOCl/OCl(-)) and monochloramine (NH(2)Cl) to mobilize mercury from dental amalgam. Two types of amalgam were used in this investigation: laboratory-prepared amalgam and samples obtained from dental-unit wastewater. For disinfectant exposure simulations, 0.5 g of either the laboratory-generated or clinically obtained amalgam waste was added to 250 mL amber bottles. The amalgam samples were agitated by end-over-end rotation at 30 rpm in the presence of 1 mg/L chlorine, 10 mg/L chlorine, 1 mg/L monochloramine, 10 mg/L monochloramine, or deionized water for intervals of 0 h, 2 h, 4 h, 8 h, and 24 h for the clinically obtained amalgam waste samples and 4 h and 24 h for the laboratory-prepared samples. Chlorine and monochloramine concentrations were measured with a spectrophotometer. Samples were filtered through a 0.45 microm membrane filter and analyzed for mercury with USEPA standard method 245.7. When the two sample types were combined, the mean mercury level in the 1 mg/L chlorine group was 0.020 mg/L (n=25, SD=0.008). The 10 mg/L chlorine group had a mean mercury concentration of 0.59 mg/L (n=25, SD=1.06). The 1 mg/L chloramine group had a mean mercury level of 0.023 mg/L (n=25, SD=0.010). The 10 mg/L chloramine group had a mean mercury level of 0.024 mg/L (n=25, SD=0.011). Independent samples t-tests showed that there was a significant difference between the natural log mercury measurements of 10 mg/L chlorine compared to those of 1 mg/L and 10 mg/L chloramine. Changing from chlorine to chloramine disinfection at water treatment plants would not be expected to produce substantial increases in dissolved mercury levels in dental-unit wastewater.

Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey.

The present study was performed to determine whether acetaminophen (paracetamol) use after the measles-mumps-rubella vaccination could be associated with autistic disorder. This case-control study used the results of an online parental survey conducted from 16 July 2005 to 30 January 2006, consisting of 83 children with autistic disorder and 80 control children. Acetaminophen use after measles-mumps-rubella vaccination was significantly associated with autistic disorder when considering children 5 years of age or less (OR 6.11, 95% CI 1.42-26.3), after limiting cases to children with regression in development (OR 3.97, 95% CI 1.11-14.3), and when considering only children who had post-vaccination sequelae (OR 8.23, 95% CI 1.56-43.3), adjusting for age, gender, mother's ethnicity, and the presence of illness concurrent with measles-mumps-rubella vaccination. Ibuprofen use after measles-mumps-rubella vaccination was not associated with autistic disorder. This preliminary study found that acetaminophen use after measles-mumps-rubella vaccination was associated with autistic disorder.

Breastfeeding, infant formula supplementation, and Autistic Disorder: the results of a parent survey.

BACKGROUND: Although Autistic Disorder is associated with several congenital conditions, the cause for most cases is unknown. The present study was undertaken to determine whether breastfeeding or the use of infant formula supplemented with docosahexaenoic acid and arachidonic acid is associated with Autistic Disorder. The hypothesis is that breastfeeding and use of infant formula supplemented with docosahexaenoic acid/arachidonic acid are protective for Autistic Disorder. METHODS: This is a case-control study using data from the Autism Internet Research Survey, an online parental survey conducted from February to April 2005 with results for 861 children with Autistic Disorder and 123 control children. The analyses were performed using logistic regression. RESULTS: Absence of breastfeeding when compared to breastfeeding for more than six months was significantly associated with an increase in the odds of having autistic disorder when all cases were considered (OR 2.48, 95% CI 1.42, 4.35) and after limiting cases to children with regression in development (OR 1.95, 95% CI 1.01, 3.78). Use of infant formula without docosahexaenoic acid and arachidonic acid supplementation versus exclusive breastfeeding was associated with a significant increase in the odds of autistic disorder when all cases were considered (OR 4.41, 95% CI 1.24, 15.7) and after limiting cases to children with regression in development (OR 12.96, 95% CI 1.27, 132). CONCLUSION: The results of this preliminary study indicate that children who were not breastfed or were fed infant formula without docosahexaenoic acid/arachidonic acid supplementation were significantly more likely to have autistic disorder.