Experience with dronabinol consumption facilitated a stimulant effect of alcohol and affected alcohol-related changes in frontal cortical endocannabinoid levels in male rats.

Combined use of cannabis and alcohol is common in adolescents. However, the extent to which such polydrug exposure affects the brain and behaviors remains under-investigated in preclinical studies. This study tested the hypothesis that combined exposure of Δ-9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, and alcohol will have additive effects on cognitive impairments and altered endocannabinoid levels in the hippocampus and frontal cortex. Male Long Evans rats were provided with daily access to cookies laced with oil or dronabinol, a synthetic THC, during adolescence. Three days after discontinuation of edible THC, the effect of orally administered 3 g/kg alcohol on Barnes maze performance was assessed. The results showed that experience with edible THC facilitated the occurrence of increased moving speed on the maze induced by repeated alcohol administration. However, contrasting to the hypothesis, the combined THC and alcohol exposure did not lead to additive deficits in learning and memory on the Barnes maze. While little effect on endocannabinoid levels was observed in the hippocampus, acute abstinence from alcohol significantly reduced endocannabinoid levels in the frontal cortex. In particular, reduction of N-oleoyl ethanolamine (OEA) and N-stearoyl ethanolamine (SEA) were robust and had an interactive effect with discontinuation from edible THC. These findings add to the scarce literature on THC and alcohol associated changes in endocannabinoid levels and provide insights to future investigations on the roles of OEA and SEA on physiology and behaviors following THC and alcohol co-exposure during adolescence.

Joint and separate exposure to alcohol and ∆9-tetrahydrocannabinol produced distinct effects on glucose and insulin homeostasis in male rats.

Cannabis and alcohol co-use is common, and the trend may increase further given the current popularity of cannabis legalization. However, the metabolic consequences of such co-use are unclear. Here, we investigated how co-administration of alcohol and ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, affects body weight and visceral adiposity, and glucose and insulin homeostasis in rats. For 16 consecutive days during adolescence, male rats drank saccharin or alcohol after receiving subcutaneous oil or THC injections in Experiment 1 and voluntarily consumed alcohol, THC edible, or both drugs in Experiment 2. Experiment 1 showed that following abstinence, drug co-exposure reduced visceral fat and the amount of insulin required to clear glucose during an oral glucose tolerance test (OGTT). In Experiment 2, rats received a high-fat diet (HFD) after 3-week abstinence. Although adolescent drug use did not interact with the HFD to worsen hyperglycemia and hyperinsulinemia during an OGTT, HFD-fed rats that co-used alcohol and THC had the lowest insulin levels 75 min after an insulin injection, suggesting an altered rate of insulin secretion and degradation. These results suggest that THC and alcohol co-exposure can distinctly alter the physiology of glucose and insulin homeostasis in a rodent model.

Diagnosis of Primary Colorectal Carcinoma with Primary Breast Cancer: Associations or Connections?

Introduction Although once very uncommon, multiple primary malignant neoplasms (MPMN) are becoming an increasingly popular subject in medical literature. With 182,000 new diagnoses per annum, breast cancer is the most frequently diagnosed cancer amongst women in the United States. Colorectal cancer remains the second most commonly diagnosed cancer in females, and the third in males worldwide. Methods In order to gather literature on synchronous and metachronous occurring breast and colon cancer, we searched PubMed using keywords such as 'colorectal cancer', 'breast cancer', and 'MPMN'. We searched through case reports, case series, clinical trials, letters to the editor, and retrospective series. We included any manuscript in English published between January 1990 and January 2019. The articles featured patients who had primary colorectal cancer with primary breast cancer. Articles featuring patients with more than two malignancies or malignancies other than colorectal and breast cancer were excluded. Furthermore, any metastatic cancers were excluded as well. This narrowed our search down from over 100 manuscripts to just four.  Results Fortunately, the prognosis was found to be no different for these patients with MPMN assuming diagnosis and treatment are performed in a timely fashion. Additionally, it appears that although a patient with one primary cancer is at a greater risk for the development of a second cancer, it is still an odd phenomenon and thus an unlikely occurrence. Conclusion Detection of one cancer increases the odds of detecting another cancer. Hence, it is important to consider the possibility of a synchronous tumor in a patient with a newly diagnosed colon tumor, as well as to not only consider disease recurrence when following up post-resection.

Combined ∆9-tetrahydrocannabinol and moderate alcohol administration: effects on ingestive behaviors in adolescent male rats.

RATIONALE: Whereas co-use of alcohol and marijuana is prevalent in adolescents, the effects of such drug co-exposure on ingestive and cognitive behaviors remain largely unexplored. We hypothesized that co-exposure to alcohol and ∆9-tetrahydrocannabinol (THC), the main psychoactive constitute of marijuana, alters feeding behavior and cognition differently from either drug alone. METHODS: Male rats received daily THC (3-20 mg/kg/day) or oil vehicle through subcutaneous injection or consumption of a cookie with access to saccharin or saccharin-sweetened alcohol during adolescence (P30-45). Barnes maze and sucrose preference tests were applied to assess spatial memory and behavioral flexibility and abstinence-related anhedonia, respectively. RESULTS: Subcutaneous THC did not affect alcohol intake but dose-dependently increased acute (3 h) chow intake and reduced weight gain. Moderate alcohol consumption reduced the acute hyperphagic effect of subcutaneous THC. By contrast, oral THC at a dose > 5 mg/kg robustly reduced alcohol intake without affecting 3-h chow intake. At this dose, some rats stopped consuming the THC-laced cookies. Furthermore, oral THC reduced weight gain, and co-exposure to alcohol alleviated this effect. Chronic subcutaneous, but not oral, THC reduced sucrose intake during abstinence. Neither treatment impaired cognitive behaviors in the Barnes maze. CONCLUSION: Moderate alcohol and THC consumption can interact to elicit unique outcomes on ingestive behaviors and energy balance. Importantly, this study established a novel model of voluntary alcohol and THC consumption for studying mechanisms underlying the consequences of adolescent onset co-use of the two drugs.