Progesterone Attenuates the Stress Response in Individuals with Alcohol Dependence and Post-Traumatic Stress Disorder - A Pilot Study.

OBJECTIVE: Evidence from laboratory studies suggests that progesterone may be effective in reducing stress and craving, and may improve cognitive performance in smokers and individuals with cocaine dependence. The objective of this study was to examine if progesterone would attenuate stress-induced craving, anxiety, affect and physiological measures, as well as improve stress-induced cognitive performance (processing speed and selective attention) in individuals diagnosed with alcohol use disorder (AUD) and post traumatic stress disorder (PTSD). METHODS: This laboratory study included (n = 13) participants who were diagnosed with current AUD and PTSD who were randomly assigned to recive either progesterone (200mg bid) or placebo in identical looking capsules for 3 days. On the fourth day they completed a laboratory session. In the morning of the test session, they received the last dose of medication and completed the rest of the laboratory procedures. The procedures included presentation in random order of personalized trauma and neutral scripts with relaxation in between. Main outcomes included measure of craving, anxiety, affect and cognitive performance. RESULTS: Consistent with other research, trauma scripts produced significantly greater increases in craving, anxiety and negative affect when compared with neutral scripts. Progesterone significantly reduced stress-induced symptoms of craving, anxiety, fear, anger and sadness but had no effect on positive emotions (joy, relaxation). Progesterone was effective in ameliorating stress-induced decreases in cognitive performance. CONCLUSIONS: The findings from this study demonstrate that progesterone can be effective in reducing stress-induced craving, anxiety and negative affect in a laboratory setting in individuals with comorbid AUD and PTSD. Interestingly, progesterone also improved cognitive performance. These findings require replication in a larger clinical trial and may have implications for treatment among individuals with AUD and PTSD.This study was registered as NCT02187224, at www.clinicaltrials.gov.

Zonisamide as an Adjunctive Treatment to Cognitive Processing Therapy for Veterans With Posttraumatic Stress Disorder and Comorbid Alcohol Use Disorder: A Pilot Study.

BACKGROUND AND OBJECTIVES: There are high rates of comorbid alcohol use disorder (AUD) among those who have posttraumatic stress disorder (PTSD). Ideally, treatment for comorbidity should address both disorders simultaneously. Zonisamide, an anticonvulsant, may be effective in decreasing alcohol use and may attenuate symptoms of PTSD. Treatment strategies can include medication in combination with a proven evidence-based psychotherapy designed to treat PTSD, such as cognitive processing therapy (CPT). METHODS: This 12-week pilot study was designed to test feasibility, acceptability, and preliminary efficacy of zonisamide (400 mg) as an adjunct to CPT for veterans with PTSD and comorbid AUD. Veterans (n = 24) with PTSD and current alcohol dependence were randomized in a 3:1 ratio to receive zonisamide or placebo in a double-blind fashion. All subjects received CPT enhanced to include sessions addressing drinking behavior. RESULTS: Subjects overall reported a significant decrease in drinking outcomes, craving, and symptoms of PTSD. Zonisamide was well-tolerated and easily administered with CPT, which was also well-tolerated. Exploratory analysis of comparison of groups suggests there was no advantage of zonisamide vs placebo in drinking or PTSD outcomes. There was a numeric but nonsignificant higher rate of abstinence with zonisamide (50%) vs placebo (33%). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: The interpretation of the results is limited by the pilot nature of this study. The combination of psychosocial treatment with medication management mimics real-world treatment. In order to isolate the individual contributions of medication vs psychotherapy a much larger study would need to be conducted. (Am J Addict 2020;29:515-524).

Thiopental Does Not Produce Hyperalgesia: A Laboratory Study Using Two Human Experimental Pain Models.

OBJECTIVE: Past investigations assessing the effects of thiopental on pain are conflicting. Although several studies demonstrate hyperalgesia as a result of barbiturate administration, others show analgesia. Our objective was to assess the effects of an infusion of the GABAA agonist thiopental, compared with placebo, in healthy participants on two subjective experimental pain paradigms: noxious electrical stimulation and intradermal capsaicin. METHODS: For electrical stimulation, the milliamps required to achieve pain threshold and tolerance were recorded, and the percent change from baseline was determined for each infusion condition. In the intradermal capsaicin condition, the area of hyperalgesia was determined by von Frey technique pre- and postinfusion, and the percent change in the area of hyperalgesia was calculated. RESULTS: Though thiopental infusion resulted in an increase in the electrical stimulation current required to elicit pain threshold or reach pain tolerance when compared with baseline, this finding was not statistically significant. In the intradermal capsaicin condition, there was a statistically significant difference in overall pre- and postinfusion pain interpretation, as measured by the McGill Pain Questionnaire (P < 0.05), but there was no significant difference in area of hyperalgesia. CONCLUSIONS: In this human study of thiopental's effects on two experimental pain models, our results show that thiopental does not induce hyperalgesia.