The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial.

IMPORTANCE: There is a pressing need for development of novel pharmacology for the treatment of Posttraumatic Stress Disorder (PTSD). Given increasing use of medical cannabis among US military veterans to self-treat PTSD, there is strong public interest in whether cannabis may be a safe and effective treatment for PTSD. OBJECTIVE: The aim of the present study was to collect preliminary data on the safety and potential efficacy of three active concentrations of smoked cannabis (i.e., High THC = approximately 12% THC and < 0.05% CBD; High CBD = 11% CBD and 0.50% THC; THC+CBD = approximately 7.9% THC and 8.1% CBD, and placebo = < 0.03% THC and < 0.01% CBD) compared to placebo in the treatment of PTSD among military veterans. METHODS: The study used a double-blind, cross-over design, where participants were randomly assigned to receive three weeks of either active treatment or placebo in Stage 1 (N = 80), and then were re-randomized after a 2-week washout period to receive one of the other three active treatments in Stage 2 (N = 74). The primary outcome measure was change in PTSD symptom severity from baseline to end of treatment in Stage 1. RESULTS: The study did not find a significant difference in change in PTSD symptom severity between the active cannabis concentrations and placebo by the end of Stage 1. All three active concentrations of smoked cannabis were generally well tolerated. CONCLUSIONS AND RELEVANCE: The present study is the first randomized placebo-controlled trial of smoked cannabis for PTSD. All treatment groups, including placebo, showed good tolerability and significant improvements in PTSD symptoms during three weeks of treatment, but no active treatment statistically outperformed placebo in this brief, preliminary trial. Additional well-controlled and adequately powered studies with cannabis suitable for FDA drug development are needed to determine whether smoked cannabis improves symptoms of PTSD. TRIAL REGISTRATION: Identifier: NCT02759185; ClinicalTrials.gov.

Posttraumatic Growth After MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder.

3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder (PTSD) has been shown to significantly reduce clinical symptomatology, but posttraumatic growth (PTG), which consists of positive changes in self-perception, interpersonal relationships, or philosophy of life, has not been studied with this treatment. Participant data (n = 60) were pooled from three Phase 2 clinical studies employing triple-blind crossover designs. Participants were required to meet DSM-IV-R criteria for PTSD with a score higher than 50 on the Clinician-Administered PTSD Scale (CAPS-IV) as well as previous inadequate response to pharmacological and/or psychotherapeutic treatment. Data were aggregated into two groups: an active MDMA dose group (75-125 mg of MDMA; n = 45) or placebo/active control (0-40 mg of MDMA; n = 15). Measures included the Posttraumatic Growth Inventory (PTGI) and the CAPS-IV, which were administered at baseline, primary endpoint, treatment exit, and 12-month follow-up. At primary endpoint, the MDMA group demonstrated more PTG, Hedges' g = 1.14, 95% CI [0.49, 1.78], p < .001; and a larger reduction in PTSD symptom severity, Hedges' g = 0.88, 95% CI [-0.28, 1.50], p < .001, relative to the control group. Relative to baseline, at the 12-month follow-up, within-subject PTG was higher, p < .001; PTSD symptom severity scores were lower, p < .001; and two-thirds of participants (67.2%) no longer met criteria for PTSD. MDMA-assisted psychotherapy for PTSD resulted in PTG and clinical symptom reductions of large-magnitude effect sizes. Results suggest that PTG may provide a new mechanism of action warranting further study.

Detection rate of quadruple-marker screening determined by clinical follow-up and registry data in the statewide California program, July 2007 to February 2009.

OBJECTIVE: To evaluate the efficiency of California's quadruple-marker screening program and construct receiver-operating characteristic (ROC) curves. METHODS: This study included the screening records of 552 941 women during July 2007 to February 2009. The screen-positive women received clinical follow-up services at state-approved centers. We used the California Chromosome Defect Registry which includes clinical, laboratory, and demographic data from the prenatal diagnostic centers, cytogenetic laboratories, hospitals, and prenatal care providers. Risk calculations, screen-positive rates (SPRs), detection rates (DRs) for chromosomal abnormalities, and 95% confidence intervals (95% CIs) were determined. ROC curves comparing the quadruple-marker to triple-marker screening were constructed. RESULTS: The DR and SPR for trisomy 21 (N = 827) during the quadruple-marker time period were 75.7% (95% CI 72.8-78.6%) and 3.75% (95% CI 3.70-3.80%) compared with 77.4% (95% CI 75.0-79.7%) and 5.4% during the triple-marker phase. The DRs were 78.2% (95% CI 75.0-81.4%) with ultrasound dating and 66.9% (95% CI 59.7-74.0%) for last-menstrual-period-dated pregnancies. For trisomy 18, triploidy, and trisomy 13, the DRs were 84.3, 95.7, and 43.5%, respectively. CONCLUSIONS: The DR for trisomy 21 in California's statewide quadruple-marker screening is very similar to the Program's previously reported DR using triple-marker screening. However, this was achieved at a lower SPR, demonstrating improved screening performance.