Posttraumatic stress disorder (PTSD) is an often chronic condition for which currently available medications have limited efficacy. Medical cannabis is increasingly used to treat patients with PTSD... Show morePosttraumatic stress disorder (PTSD) is an often chronic condition for which currently available medications have limited efficacy. Medical cannabis is increasingly used to treat patients with PTSD; however, evidence for the efficacy and safety of cannabinoids is scarce. To learn more about patients' opinions on and experiences with medical cannabis, we organized a focus group discussion among military veterans (N = 7) with chronic PTSD who were treated with medical cannabis. Afterwards, some of their partners (N = 4) joined the group for an evaluation, during which they shared their perspective on their partner's use of medical cannabis. Both sessions were audio-recorded, transcribed verbatim, and analyzed by means of qualitative content analysis. Five overarching themes were identified. The first four themes related to the different phases of medical cannabis use - namely, 1) Consideration; 2) Initiation; 3) Usage; and 4) Discontinuation. The fifth theme related to several general aspects of medical cannabis use. Patients used medical cannabis to manage their symptoms and did not experience an urge to "get high." They used a variety of different cannabis strains and dosages and reported several therapeutic effects, including an increased quality of sleep. Furthermore, discussions about the experienced stigma surrounding cannabis generated insights with implications for the initiation of medical cannabis use. These results underscore the value of qualitative research in this field and are relevant for the design of future clinical trials on the use of medical cannabis for the treatment of PTSD. (c) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/) Show less
Bisson, J.I.; Deursen, R. van; Hannigan, B.; Kitchiner, N.; Barawi, K.; Jones, K.; ... ; Vermetten, E. 2020
Objective To explore the potential efficacy of multi-modular motion-assisted memory desensitization and reprocessing (3MDR) in British military veterans with treatment-resistant service-related... Show moreObjective To explore the potential efficacy of multi-modular motion-assisted memory desensitization and reprocessing (3MDR) in British military veterans with treatment-resistant service-related PTSD. Methods Exploratory single-blind, randomized, parallel arm, cross-over controlled trial with nested process evaluation to assess fidelity, adherence and factors that influence outcome. Results A total of 42 participants (all male) were randomized with 83% retention at 12 weeks and 86% at 26 weeks. The difference in mean Clinician-Administered PTSD Scale for DSM-5 scores between the immediate and delayed 3MDR arms was -9.38 (95% CI -17.33 to -1.44,P = 0.021) at 12 weeks and -3.59 (-14.39 to 7.20,P = 0.513) at 26 weeks when both groups had received 3MDR. The likely effect size of 3MDR was found to be 0.65. Improvements were maintained at 26-week follow-up. 3MDR was found to be acceptable to most, but not all, participants. Several factors that may impact efficacy and acceptability of 3MDR were identified. Conclusion 3MDR is a promising new intervention for treatment-resistant PTSD with emerging evidence of effect. Show less
Krediet, E.; Bostoen, T.; Breeksema, J.; Schagen, A. van; Passie, T.; Vermetten, E. 2020
There are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line... Show moreThere are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line treatment for PTSD. Yet, even after psychotherapy, PTSD often remains a chronic illness, with high rates of psychiatric and medical comorbidity. Meanwhile, the search for and development of drugs with new mechanisms of action has stalled. Therefore, there is an urgent need to explore not just novel compounds but novel approaches for the treatment of PTSD. A promising new approach involves the use of psychedelic drugs. Within the past few years, 2 psychedelics have received breakthrough designations for psychiatric indications from the US Food and Drug Administration, and several psychedelics are currently being investigated for the treatment of PTSD. This review discusses 4 types of compounds: 3,4-methylenedioxymethamphetamine, ketamine, classical psychedelics (e.g., psilocybin and lysergic acid diethylamide), and cannabinoids. We describe the therapeutic rationale, the setting in which they are being administered, and their current state of evidence in the treatment of PTSD. Each compound provides unique qualities for the treatment of PTSD, from their use to rapidly target symptoms to their use as adjuncts to facilitate psychotherapeutic treatments. Several questions are formulated that outline an agenda for future research. Show less
Background Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450... Show moreBackground Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whether DNA methylation profiles are associated with the development of PTSD. A total of 123 PTSD cases and 143 trauma-exposed controls were included in the analyses. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis in a two-stage design. In stage one, we jointly analyzed data of two new cohorts (N = 126 and 78) for gene discovery, and sought to replicate significant findings in a third, previously published cohort (N = 62) to assess the robustness of our results. In stage 2, we aimed at maximizing power for gene discovery by combining all three cohorts in a meta-analysis. Results Stage 1 analyses identified four CpG sites in which, conditional on pre-deployment DNA methylation, post-deployment DNA methylation was significantly associated with PTSD status after epigenome-wide adjustment for multiple comparisons. The most significant (intergenic) CpG cg05656210 (p = 1.0 x 10(-08)) was located on 5q31 and significantly replicated in the third cohort. In addition, 19 differentially methylated regions (DMRs) were identified, but failed replication. Stage 2 analyses identified three epigenome-wide significant CpGs, the intergenic CpG cg05656210 and two additional CpGs located in MAD1L1 (cg12169700) and HEXDC (cg20756026). Interestingly, cg12169700 had an underlying single nucleotide polymorphism (SNP) which was located within the same LD block as a recently identified PTSD-associated SNP in MAD1L1. Stage 2 analyses further identified 12 significant differential methylated regions (DMRs), 1 of which was located in MAD1L1 and 4 were situated in the human leukocyte antigen (HLA) region. Conclusions This study suggests that the development of combat-related PTSD is associated with distinct methylation patterns in several genomic positions and regions. Our most prominent findings suggest the involvement of the immune system through the HLA region and HEXDC, and MAD1L1 which was previously associated with PTSD. Show less
Gelderen, M.J. van; Nijdam, M.J.; Dubbink, G.E.; Sleijpen, M.; Vermetten, E. 2020
Background: A novel intervention, Multi-modular motion-assisted memory desensitization and reconsolidation (3MDR), aims to reduce avoidance and improve engagement for patients with posttraumatic... Show moreBackground: A novel intervention, Multi-modular motion-assisted memory desensitization and reconsolidation (3MDR), aims to reduce avoidance and improve engagement for patients with posttraumatic stress disorder (PTSD) who did not sufficiently respond to previous treatments. It has been found to effectively reduce PTSD symptoms for veterans with treatment-resistant PTSD. Symptomatic measures alone might not capture all treatment effects, and addition of qualitative outcomes may provide deeper understanding of treatment processes and treatment-induced changes.Objective: To study the perspectives of veterans with treatment-resistant PTSD on 3MDR treatment processes and effects and explore the relation of their experiences to PTSD symptom improvement.Method: A convergent parallel mixed methods design was applied. For the qualitative part, open-ended question interviews were conducted until data saturation was reached (N = 10). Thematic analysis, rooted in grounded theory, was performed. Quantitative data included pre- to posttreatment responder status based on a structured clinical interview for PTSD.Results: Treatment processes endorsed by the veterans were engaging, regulating distress, feeling supported, facing traumatic memories, allowing emotions, associating, and disengaging from trauma. In terms of effects, veterans reported positive changes following 3MDR, including openness, new learning, self-understanding, closure, and reintegration. High comparability across themes was observed for responders and non-responders, except for the themes closure and reintegration, which were reported more often or more in depth by responders.Conclusions: Veterans indicated 3MDR treatment processes that complied with its aims of breaking through avoidance and increasing engagement, thereby facilitating traumatic memory retrieval and processing. However, this did not necessarily translate into PTSD symptom improvement for all veterans. Walking towards trauma-related pictures was highlighted as unique component of 3MDR and connected to specific treatment processes and effects. Positive changes following 3MDR were experienced outside the domain of PTSD symptom improvement, implicating that 3MDR may beneficially impact veterans beyond symptom changes alone. Show less
