Product labeling accuracy and contamination analysis of commercially available cannabidiol product samples.

Background and objective: Commercially available cannabidiol (CBD) products are increasingly being used for medicinal purposes, including for the treatment of various neurological conditions, but there are growing concerns around adherence to quality control measures that protect consumers. This study was conducted to assess the purity and label accuracy of commercially available CBD products. Methods: Commercially available CBD products were chosen from the open stream of commerce in the United States based on formulations as a tincture, gummy, vape, or topical product. Cannabinoid concentrations were analyzed to verify label accuracy including "full spectrum," "broad spectrum," and "CBD isolate" claims on the product label. Analysis for the presence of contaminants included evaluation for heavy metals, pesticides, and residual solvents. Labeled and actual total amounts of CBD and levels of impurities such as heavy metals, residual solvents, and pesticides were measured. Results: A total of 202 CBD products (100 tinctures, 48 gummies, 34 vape products, and 20 topicals) were chosen to represent a broad sample in the United States. Of the products tested (full spectrum, n = 84; broad spectrum, n = 28; CBD isolate, n = 37), 26% did not meet the definition for product type claimed on the packaging. The majority of products (74%) deviated from their label claim of CBD potency by at least 10%. Heavy metals were detected 52 times across 44 of the 202 products tested, with lead being the most prevalent heavy metal. Residual solvents were detected 446 times across 181 of 202 products, with the highest concentrations reported for hexane, m/p-xylene, methanol, and o-xylene. Of 232 pesticides tested, 26 were found 55 times across 30 products. A total of 3% of heavy metals, 1% of residual solvents, and 1% of pesticides violated >1 regulatory threshold. Discussion: This study demonstrated that the majority of commercially available CBD products tested within the current study are inaccurately labeled. Heavy metals, residual solvents, and pesticides were found in several products, some of which violated regulatory thresholds. Thus, uniform compliance with CBD quality control measures is lacking and raises consumer protection concerns. Improved regulatory oversight of this industry is recommended.

Repeated toluene exposure leads to neuroadaptation in dopamine release mechanisms within the nucleus accumbens core.

BACKGROUND: Intentionally inhaling volatile organic solvent like toluene for its intoxicating effects continues to be a public health concern. While repeated abuse of toluene has deleterious behavioral and health effects, little is known about the actions of toluene on the dopaminergic neurotransmitter system within the central nervous system. METHOD: The present study employed complementary neurochemical techniques of slice fast-scan cyclic voltammetry (FSCV) and in vivo microdialysis, to assess dopamine (DA) dynamics immediately after repeated exposure to 2000- or 4000-ppm toluene. DA D3 autoreceptor functionality, measured by FSCV with pharmacological manipulations and brain tissue content analysis with high performance liquid chromatography, were also used to account for the changes in the DA dynamics. RESULTS: Toluene-exposed mice had decreased stimulated DA release only in the nucleus accumbens core immediately after seven days of repeated exposure. DA uptake was decreased in the core only after 2000-ppm exposure. The differences in stimulated DA release were not attributed to alterations in intraneuronal DA levels as measured by tissue content analysis. Basal extracellular DA levels were not significantly different between the air- and toluene-treated mice. However, following an additional toluene exposure, mice had elevated extracellular DA levels in the nucleus accumbens during recovery. This potentiation in extracellular accumbal DA levels was further heightened following potassium stimulation. The accumbal DA D3 autoreceptor function did not appear to play a role as a potential mediator for these differences. CONCLUSION: Our FSCV and microdialysis results suggest a neuroadaptation in DA release mechanics within the nucleus accumbens, but the exact neuronal mechanism of toluene's impact remains elusive.

Lead and cadmium contamination in a large sample of United States infant formulas and baby foods.

Data is limited on lead and cadmium contamination in baby food, a population uniquely susceptible to the toxic effects of heavy metals. The goal of this study was to examine lead and cadmium concentrations in a large convenience sample of US baby foods. We identified the number of baby food product samples that exceeded US FDA and California Proposition 65 limits for daily lead consumption across a range of servings/calories, and the number of samples that exceeded World Health Organization and California Proposition 65 limits for daily cadmium consumption across a range of servings/calories. In total, 564 baby foods were tested across infant and toddler formula, cereals, meals, juices/drinks, jars, pouches, snacks, and electrolyte water. ICP-MS analysis of lead and cadmium was completed using a modified version of EPA method 6020A. Samples were analyzed using kinetic energy distribution mode. Lead was detected in 37% of samples (median = non-detect, 75% = 5.6, maximum = 183.6 µg/kg), and cadmium in 57% (25% = non-detect, median = 2.8, 75% = 9.5, maximum = 103.90 µg/kg). Of 91 infant formula samples, none exceeded FDA lead consumption guidelines in 31 oz, but 22% exceeded the Proposition 65 lead guidelines, 23% exceeded the Proposition 65 cadmium guidelines, and 14% exceeded the WHO tolerable cadmium intake levels for a four-month-old baby. In the solid baby food samples, 1% exceeded FDA lead guidelines in two servings (26% exceeded CA Proposition 65 limits), 3% in 300 cal (34% exceeded CA Proposition 65 limits). For cadmium, 6% exceeded Proposition 65 guidelines in two servings, 8% in 300 cal. There was no association between whether the product was certified organic and its heavy metal concentration. Products containing rice were higher in both lead and cadmium concentrations. Further research is needed to understand the long-term health effects of this chronic daily low level heavy metal exposure in babies.

Abstinence following toluene exposure increases anxiety-like behavior in mice.

The intentional misuse of volatile solvents like toluene is a persistent public health concern. Limited clinical data suggest that chronic inhalant abusers may experience signs of withdrawal, including anxiety. Behavioral withdrawal from toluene has not been examined in a preclinical model. In the current study, young adult male Swiss Webster mice were exposed to either 5000-ppm toluene vapor or air (0ppm) for 30min or 24h. Mice were tested in a battery of four behavioral tasks reflective of anxiety either immediately (0h), 24h, or 72h after the toluene exposure. Mice exposed briefly (30min) to toluene showed decreases in anxiety-like behaviors, whereas mice abstinent from toluene for 24h after a prolonged (24-h) exposure, displayed increases in anxiety-like behaviors. These increases in anxiety-like behavior were not observed 72h post toluene. However, a brief re-exposure to toluene (30min at 5000ppm) immediately before testing 24h after the prolonged exposure ameliorated behavioral differences on the plus maze task. These results of 1) decreased anxiety-like behavior immediately following acute toluene, and 2) the contrasting increase in anxiety-like behavior during abstinence from a prolonged toluene exposure, and 3) the amelioration of increases in an anxiety-like behavior following toluene re-exposure, are consistent with an interpretation of withdrawal from the single 24-hr toluene exposure. These findings support clinical reports of increased anxiety during abstinence following periods of toluene use/abuse. The results also imply that experiencing anxiety during withdrawal from toluene may contribute to the persistent use of inhalants and may be relevant to clinical treatment of inhalant abuse/addiction.

Molecular, Behavioral, and Physiological Consequences of Methamphetamine Neurotoxicity: Implications for Treatment.

Understanding the relationship between the molecular mechanisms underlying neurotoxicity of high-dose methamphetamine (METH) and related clinical manifestations is imperative for providing more effective treatments for human METH users. This article provides an overview of clinical manifestations of METH neurotoxicity to the central nervous system and neurobiology underlying the consequences of administration of neurotoxic METH doses, and discusses implications of METH neurotoxicity for treatment of human abusers of the drug.

Toluene's effects on activity and extracellular dopamine in the mouse are altered by GABAA antagonism.

The abuse of inhalants like toluene continues to be widespread around the world, especially among children and teenagers. Despite its frequency of misuse, the dynamics between dopamine (DA) and gamma-aminobutyric acid (GABA) in response to toluene exposure remains unclear. To further decipher toluene's actions, we used a dynamic exposure system in combination with microdialysis to examine in vivo the effects of acutely inhaled toluene on DA release within the mouse caudate putamen (CPu). Results show that toluene inhalation produced increases in DA levels and locomotor activity. In mice that were pretreated with the GABAA antagonist, bicuculline, there was no change in the locomotor response during toluene but activity was potentiated following toluene exposure. Bicuculline pretreatment increased extracellular DA levels during toluene exposure, suggesting that DA and GABA-releasing neuron interaction may play a role in the rewarding properties of toluene.

Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer's Disease (AD).

BACKGROUND AND PURPOSE: To investigate if cranial X-irradiation reduces amyloid-ß (Aß) plaques and influences cognitive function in a transgenic mouse model of AD. METHODS AND MATERIALS: B6.Cg-Tg (APPswePSEN1dE9)85Dbo/J AD-prone mice were given cranial X-irradiation. The number of Aß plaques, along with expression of AD specific genes (84 genes: Mouse Alzheimer's Disease RT(2) Profiler), radiation-associated cytokines (Milliplex MAP Mouse Cytokine Chemokine Immunoassay) and immunohistochemistry (IL10, IL-1ß, Iba1 CD45) was assessed. Behavioral testing was performed to relate changes in Aß burden to cognitive function using a Morris water-maze task. RESULTS: Single X-ray doses reduced the number (p=0.002) and size (p=0.01) of Aß plaques. Low-dose fractionation produced greater 50.6% (1 Gy × 10), 72% (2 Gy × 5) and 78% (2 Gy × 10) reductions. Irradiation was associated with gene (Pkp4, 1.5-fold, p=0.004) and proteomic (MIP-2, 8-fold, p=0.0024) changes at 24-48 h. Microglia increased at 4 weeks post-irradiation (p=0.001). The reduction in Aß burden (2 Gy × 5) was associated with cognitive improvement (p=0.012). CONCLUSION: This is the first report that a clinically relevant course of external beam irradiation (2 Gy × 5) produces a significant reduction in AD-associated amyloid-ß plaques with a subsequent improvement in cognitive function. However, longer-term studies are needed to define the precise underlying mechanism and longevity of this response.