A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Reishi Mushroom (Ganoderma lucidum), Stinging Nettle (Urtica dioica), and Epimedium (Epimedium sagittatum)

This report is third in a three-part clinical trial series screening potential treatments for Gulf War Illness (GWI). The goal of the project was to rapidly identify agents to prioritize for further efficacy research. We used a placebo-controlled, pseudo-randomized, crossover design to test the effects of reishi mushroom (Ganoderma lucidum), stinging nettle (Uritca dioica), and epimedium (Epimedium sagittatum) in 29 men with GWI. Participants completed 30 days of symptom reports for baseline, then a botanical line consisting of 30 days of placebo, followed by 30 days each of lower-dose and higher-dose botanical. After completing a botanical line, participants were randomized to complete the protocol with another botanical, until they completed three botanical trials. GWI symptom severity, pain, and fatigue were contrasted between the four conditions (baseline, placebo, lower-dose, higher dose) using linear mixed models. GWI symptom severity was unchanged from placebo in the reishi lower-dose condition (p = 0.603), and was higher in the higher-dose condition (p = 0.012). Symptom severity was not decreased from placebo with lower-dose stinging nettle (p = 0.604), but was significantly decreased with higher-dose stinging nettle (p = 0.048). Epimedium showed no significant decreases of GWI symptoms in the lower (p = 0.936) or higher (p = 0.183) dose conditions. Stinging nettle, especially at higher daily dosages, may help reduce the symptoms of GWI. Epimedium does not appear to beneficially affect GWI symptom severity, and reishi may exaggerate symptoms in some GWI sufferers. These results are in a small sample and are preliminary. Further research is required to determine if stinging nettle is indeed helpful for the treatment of GWI, and what dosage is optimal. This trial was registered on ClinicalTrials.gov (NCT02909686).

The Effects of Strain and Estrous Cycle on Heroin- and Sucrose-Maintained Responding in Female Rats

Heroin intake decreases during the proestrus phase of the estrous cycle in female, Long-Evans rats. The purpose of this study was to (1) determine if proestrus-induced decreases in heroin intake extend across rat strains and (2) determine if proestrus-induced decreases in responding extend to a nondrug reinforcer. Female rats were implanted with intravenous catheters and trained to self-administer heroin. Estrous cycle was tracked daily for the duration of the study. During testing, Lewis, Sprague-Dawley, and Long Evans rats self-administered low (0.0025 mg/kg) and high (0.0075 mg /kg) doses of heroin (Experiment 1) and then self-administered sucrose (Experiment 2) on fixed ratio (FR1) schedules of reinforcement. Heroin intake decreased significantly during proestrus in all three rat strains under at least one dose condition; however, sucrose intake did not decrease during proestrus in any strain. These data indicate that responding maintained by heroin, but not a nondrug reinforcer, significantly decreases during proestrus in female rats and that these effects are consistent across rat strain.

Ability to Propose Optimal Prosthetic Rehabilitation can be Improved by Discussion between the Dentist and Radiation Oncologist Regarding Upstream Dosimetry

Objective Improvement of dental rehabilitation for patients who have undergone radiation therapy requires knowledge of the dose in the maxillary and mandible bones. Materials and Methods Forty-three patients with head and neck cancers underwent evaluation for dental rehabilitation before radiation treatment dosimetry. The delivered dose to the maxilla and mandible was determined. From the dose data in the literature, three levels of risk of implant failure were defined. According to the delivered doses, the authors calculated the percentage of patients who could be fully rehabilitated with an implant, as proposed by the dentist before radiation planning. Results Before dosimetry calculation, all of the completely edentulous arches and 94 partially edentulous (PESs) sextants could be optimally rehabilitated. After dose calculation, among the 14 arches of 7 patients who were completely edentulous, according to the mean and maximal delivered doses, 11 arches (78.6%) and 7 arches (50%) could receive an optimal prosthesis, respectively. For the three patients, who were PESs but with one arch that was completely edentulous, according to the mean and maximal delivered doses, one arch for each dose condition could receive an optimal prosthesis. Among the 94 PESs sextants, according to the mean and maximal delivered doses, 41 (43.6%) and 24 (25.5%) sextants could receive an optimal prosthesis, respectively. Conclusion By determining the sites of implantation before dosimetry, the radiation oncologist could shield specified areas, potentially improving the possibilities for dental rehabilitation. The dialogue between the dentist and the radiation oncologist can improve the possibilities for implants and decrease the risk of unsafe implantation.

Evaluation of the reinforcing and subjective effects of heroin in combination with dextromethorphan and quinidine

Objective: Studies have suggested that the N-methyl-D-aspartate antagonist dextromethorphan may be useful in the treatment of opioid dependence.Design: This double-blinded, placebo-controlled inpatient study evaluated the effects of 0, 30, and 60 mg of dextromethorphan and quinidine (DMQ) on the reinforcing and subjective effects of heroin in recently detoxified heroin abusers.Participants: Nine heroin-dependent participants were admitted and then detoxified from heroin over the course of several days.Interventions: Participants were subsequently stabilized on 0, 30, or 60 mg of DMQ. Each dose of DMQ was administered for two consecutive weeks, and the effects of heroin (0, 12.5, and 50 mg) were studied under each DMQ maintenance dose condition. DMQ and heroin dose were administered in random order both within and between participants.Results: Planned comparisons revealed statistically significant increases in progressive ratio breakpoint values and positive subjective ratings as a function of heroin dose. There were no consistent changes in any of the responses as a function of DMQ maintenance dose, other than a modest reduction in craving.Conclusions: In summary, results from this study suggest that maintenance on dextromethorphan in combination with quinidine has a limited role in the treatment of opioid dependence.

Dose Response of Whey Protein Isolate in Addition to a Typical Mixed Meal on Blood Amino Acids and Hormonal Concentrations

The purpose was to investigate the effects of a controlled typical 1-day diet supplemented with two different doses of whey protein isolate on blood amino acid profiles and hormonal concentrations following the final meal. Nine males (age: 29.6 ± 6.3 yrs) completed four conditions in random order: a control (C) condition of a typical mixed diet containing ~10% protein (0.8 g·kg–1), 65% carbohydrate, and 25% fat; a placebo (P) condition calorically matched with carbohydrate to the whey protein conditions; a low-dose condition of 0.8 grams of whey protein isolate per kilogram body mass per day (g·kg–1·d–1; W1) in addition to the typical mixed diet; or a high-dose condition of 1.6 g·kg–1·d–1 (W2) of supplemental whey protein in addition to the typical mixed diet. Following the final meal, significant (p < .05) increases in total amino acids, essential amino acids (EAA), branch-chained amino acids (BCAA), and leucine were observed in plasma with whey protein supplementation while no changes were observed in the control and placebo conditions. There was no significant group difference for glucose, insulin, testosterone, cortisol, or growth hormone. In conclusion, supplementing a typical daily food intake consisting of 0.8 g of protein·kg–1·d–1 with a whey protein isolate (an additional 0.8 or 1.6 g·kg–1·d–1) significantly elevated total amino acids, EAA, BCAA, and leucine but had no effect on glucose, insulin, testosterone, cortisol, or growth hormone following the final meal. Future acute and chronic supplementation research examining the physiological and health outcomes associated with elevated amino acid profiles is warranted.