OPEN Foundation

Anxiety disorders / PTSD

How to Change Your Mind: The New Science of Psychedelics

How to Change Your Mind: The New Science of Psychedelics. Michael Pollan. The Penguin Press. ISBN: 9781594204227

A highly accessible and enjoyable read through the history of psychedelic research and use starting in the 1960s up to the present day. Pollan applies his quintessential experiential journalism approach to various psychedelic substances – starting off hesitantly, as he weaves through the research and has several personal experiences, Pollan becomes a measured advocate for the power psychedelics have to change our minds and more.

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Posttraumatic Stress Disorder After a Psychedelic Experience, a Case Report

Abstract

In the last 2 decades, there is a renaissance in the scientific investigation of the therapeutic potential of psychedelic compounds. It is studied for the treatment of many psychiatric disorders, including posttraumatic stress disorder. The treatment is always done in the setting of psychedelic-assisted psychotherapy. A little is known about the potential effects, outside of the setting of psychedelic-assisted psychotherapy, on people diagnosed with a mental disorder or have a significant trauma history. In this case report, we present a young man who developed posttraumatic stress disorder after a psychedelic experience, induced by both Lysergic Acid Diethylamide (LSD) and N, N Dimethyltryptamine (DMT). In the psychedelic experience, a repressed memory of childhood sexual abuse was recovered. To our knowledge, this is the first report on posttraumatic stress disorder onset after a psychedelic experience. We believe that this case report is important since the history of trauma is prevalent among individuals with substance use disorder. Medical staff that treat people with either substance use disorder or trauma should be familiar with irregular presentations, such as the one described in this case.

Rubin-Kahana, D. S., Hassan, A. N., & Le Foll, B. (2021). Posttraumatic Stress Disorder After a Psychedelic Experience, a Case Report. Journal of addiction medicine, 15(3), 248–251. https://doi.org/10.1097/ADM.0000000000000734

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Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes

Abstract

Mescaline is a naturally occurring psychoactive alkaloid that has been used as a sacrament by Indigenous populations in spiritual ritual and healing ceremonies for millennia. Despite promising early preliminary research and favorable anecdotal reports, there is limited research investigating mescaline’s psychotherapeutic potential. We administered an anonymous online questionnaire to adults (N = 452) reporting use of mescaline in naturalistic settings about mental health benefits attributed to mescaline. We assessed respondents’ self-reported improvements in depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol and drug use disorders (AUD and DUD). Of the respondents reporting histories of these clinical conditions, most (68-86%) reported subjective improvement following their most memorable mescaline experience. Respondents who reported an improvement in their psychiatric conditions reported significantly higher ratings of acute psychological factors including mystical-type, psychological insight, and ego dissolution effects compared to those who did not report improvements (Cohen’s d range 0.7 – 1.5). Many respondents (35-50%) rated the mescaline experience as the single or top five most spiritually significant or meaningful experience(s) of their lives. Acute experiences of psychological insight during their mescaline experience were associated with increased odds of reporting improvement in depression, anxiety, AUD and DUD. Additional research is needed to corroborate these preliminary findings and to rigorously examine the efficacy of mescaline for psychiatric treatment in controlled, longitudinal clinical trials.

Agin-Liebes, G., Haas, T. F., Lancelotta, R., Uthaug, M. V., Ramaekers, J. G., & Davis, A. K. (2021). Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes. ACS pharmacology & translational science, 4(2), 543–552. https://doi.org/10.1021/acsptsci.1c00018

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Pharmacological-assisted Psychotherapy for Post-Traumatic Stress Disorder: a systematic review and meta-analysis

Abstract

Background: Pharmacological-assisted psychotherapies, using conventional and novel drug agents, are increasingly being used both in clinical and experimental research settings, respectively. Objective: To determine the efficacy of conventional and novel pharmacological-assisted psychotherapies in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised-controlled trials were undertaken; 21 studies were included. Results: MDMA-assisted therapy was found to statistically superior to active and inactive placebo-assisted therapy in reduction of PTSD symptoms (standardised mean difference -1.09, 95% CI -1.60 to -0.58). There was no evidence of superiority over placebo for any other intervention. Conclusions: MDMA-assisted therapy demonstrated an impressive effect size; however, it is difficult to have confidence at this stage in this intervention due to the small numbers of participants included, and more research in this area is needed. There was no evidence to support the efficacy of any other drug-assisted interventions.

Hoskins, M. D., Sinnerton, R., Nakamura, A., Underwood, J., Slater, A., Lewis, C., Roberts, N. P., Bisson, J. I., Lee, M., & Clarke, L. (2021). Pharmacological-assisted Psychotherapy for Post-Traumatic Stress Disorder: a systematic review and meta-analysis. European journal of psychotraumatology, 12(1), 1853379. https://doi.org/10.1080/20008198.2020.1853379

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A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis

Abstract

Rationale: Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials.

Objective: To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD.

Methods: Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck’s Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within 7 days of intervention.

Results: Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75 mg (MD -46.90; 95% (confidence intervals) CI -58.78, -35.02), 125 mg (MD -20.98; 95% CI -34.35, -7.61) but not 100 mg (MD -12.90; 95% CI -36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD -33.20; 95% CI -40.53, -25.87). A significant decrease in BDI when compared to active placebo (MD -10.80; 95% CI -20.39, -1.21) was only observed at 75 mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after 7 days.

Conclusion: These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck’s Depression Inventory. Better powered RCTs are required to investigate further.

Illingworth, B. J., Lewis, D. J., Lambarth, A. T., Stocking, K., Duffy, J. M., Jelen, L. A., & Rucker, J. J. (2021). A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis. Journal of psychopharmacology (Oxford, England), 35(5), 501–511. https://doi.org/10.1177/0269881120965915

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MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial

Abstract

Cognitive-behavioural conjoint therapy (CBCT) for PTSD has been shown to improve PTSD, relationship adjustment, and the health and well-being of partners. MDMA (3,4-methylenedioxymethamphetamine) has been used to facilitate an individual therapy for PTSD. This study was an initial test of the safety, tolerability, and efficacy of MDMA-facilitated CBCT. Six couples with varying levels of baseline relationship satisfaction in which one partner was diagnosed with PTSD participated in a condensed version of the 15-session CBCT protocol delivered over 7 weeks. There were two sessions in which both members of the couple were administered MDMA. All couples completed the treatment protocol, and there were no serious adverse events in either partner. There were significant improvements in clinician-assessed, patient-rated, and partner-rated PTSD symptoms (pre- to post-treatment/follow-up effect sizes ranged from d = 1.85-3.59), as well as patient depression, sleep, emotion regulation, and trauma-related beliefs. In addition, there were significant improvements in patient and partner-rated relationship adjustment and happiness (d =.64-2.79). These results are contextualized in relation to prior results from individual MDMA-facilitated psychotherapy and CBCT for PTSD alone. MDMA holds promise as a facilitator of CBCT to achieve more robust and broad effects on individual and relational functioning in those with PTSD and their partners.

Monson, C. M., Wagner, A. C., Mithoefer, A. T., Liebman, R. E., Feduccia, A. A., Jerome, L., Yazar-Klosinski, B., Emerson, A., Doblin, R., & Mithoefer, M. C. (2020). MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial. European journal of psychotraumatology, 11(1), 1840123. https://doi.org/10.1080/20008198.2020.1840123

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Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies

Abstract

Objective: To conduct a systematic review of modern-era (post-millennium) clinical studies assessing the therapeutic effects of serotonergic psychedelics drugs for mental health conditions. Although the main focus was on efficacy and safety, study characteristics, duration of antidepressants effects across studies, and the role of the subjective drug experiences were also reviewed and presented.

Method: A systematic literature search (1 Jan 2000 to 1 May 2020) was conducted in PubMed and PsychINFO for studies of patients undergoing treatment with a serotonergic psychedelic.

Results: Data from 16 papers, representing 10 independent psychedelic-assisted therapy trials (psilocybin = 7, ayahuasca = 2, LSD = 1), were extracted, presented in figures and tables, and narratively synthesized and discussed. Across these studies, a total of 188 patients suffering either cancer- or illness-related anxiety and depression disorders (C/I-RADD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD) or substance use disorder (SUD) were included. The reviewed studies established feasibility and evidence of safety, alongside promising early data of efficacy in the treatment of depression, anxiety, OCD, and tobacco and alcohol use disorders. For a majority of patients, the therapeutic effects appeared to be long-lasting (weeks-months) after only 1 to 3 treatment session(s). All studies were conducted in line with guidelines for the safe conduct of psychedelic therapy, and no severe adverse events were reported.

Conclusion: The resurrection of clinical psychedelic research provides early evidence for treatment efficacy and safety for a range of psychiatric conditions, and constitutes an exciting new treatment avenue in a health area with major unmet needs.

Andersen, K., Carhart-Harris, R., Nutt, D. J., & Erritzoe, D. (2021). Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies. Acta psychiatrica Scandinavica, 143(2), 101–118. https://doi.org/10.1111/acps.13249

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Combining Ketamine, Brain Stimulation (rTMS) and Mindfulness Therapy (TIMBER) for Opioid Addiction

Abstract

Opioid addiction in the United States currently presents a national crisis despite availability of different treatments. Prior findings suggest that both repetitive transcranial magnetic stimulation (rTMS) and subanesthetic dose of ketamine are efficacious in patients with opioid use disorders (OUD) when administered in isolation. However, their therapeutic value may be undermined by varying clinical responses that tend to dissipate with treatment cessation. There has been no study to date that has used a combination of both for OUD, and there are still many unanswered questions with respect to both. TIMBER (Trauma Interventions using Mindfulness Based Extinction and Reconsolidation of memories) therapy attempts to alter the expression of emotionally charged memories such as traumatic memories, and has been successfully tried in chronic post-traumatic stress disorder (PTSD) and in combination with memory-altering pharmacotherapy like ketamine infusion. By a combination of extinction and reconsolidation of memory approaches, TIMBER works to not over-flood and/or retraumatize as is seen in other treatment approaches. TIMBER involves a balanced combination of both the memory extinction and memory reconsolidation approaches (rather than extinction-only approaches) which explains its superior efficacy in PTSD and benefit in substance use disorders.

Pradhan, B., & Rossi, G. (2020). Combining Ketamine, Brain Stimulation (rTMS) and Mindfulness Therapy (TIMBER) for Opioid Addiction. Cureus, 12(11), e11798. https://doi.org/10.7759/cureus.11798

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Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy

Abstract

Rationale: MDMA-assisted psychotherapy is under investigation as a novel treatment for posttraumatic stress disorder (PTSD). The primary mechanism of action of MDMA involves the same reuptake transporters targeted by antidepressant medications commonly prescribed for PTSD.

Objectives: Data were pooled from four phase 2 trials of MDMA-assisted psychotherapy. To explore the effect of tapering antidepressant medications, participants who had been randomized to receive active doses of MDMA (75-125 mg) were divided into two groups (taper group (n = 16) or non-taper group (n = 34)).

Methods: Between-group comparisons were made for PTSD and depression symptom severity at the baseline and the primary endpoint, and for peak vital signs across two MDMA sessions.

Results: Demographics, baseline PTSD, and depression severity were similar between the taper and non-taper groups. At the primary endpoint, the non-taper group (mean = 45.7, SD = 27.17) had a significantly (p = 0.009) lower CAPS-IV total scores compared to the taper group (mean = 70.3, SD = 33.60). More participants in the non-taper group (63.6%) no longer met PTSD criteria at the primary endpoint than those in the taper group (25.0%). The non-taper group (mean = 12.7, SD = 10.17) had lower depression symptom severity scores (p = 0.010) compared to the taper group (mean = 22.6, SD = 16.69). There were significant differences between groups in peak systolic blood pressure (p = 0.043) and diastolic blood pressure (p = 0.032).

Conclusions: Recent exposure to antidepressant drugs that target reuptake transporters may reduce treatment response to MDMA-assisted psychotherapy.

Feduccia, A. A., Jerome, L., Mithoefer, M. C., & Holland, J. (2021). Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy. Psychopharmacology, 238(2), 581–588. https://doi.org/10.1007/s00213-020-05710-w

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The potential use of N-methyl-3,4-methylenedioxyamphetamine (MDMA) assisted psychotherapy in the treatment of eating disorders comorbid with PTSD

Abstract

Despite advances in the field, eating disorders (EDs) remain very challenging disorders to treat, especially when comorbid with posttraumatic stress disorder (PTSD). N-methyl-3,4-methylenedioxyamphetamine (MDMA)-assisted psychotherapy for treatment refractory PTSD shows great promise, with two-thirds of participants achieving full remission at 1 year or more at follow-up. PTSD is a common comorbidity associated with EDs, and patients with EDs and PTSD (ED-PTSD) are reported to have higher severities of illness, greater comorbidities, higher treatment dropouts, and poorer outcomes. We hypothesize that MDMA-assisted psychotherapy will be efficacious in the ED-PTSD population for both ED and PTSD symptoms. The rationales for and proposed mechanisms of MDMA-assisted psychotherapy for ED-PTSD are considered from neurobiological, psychological and social perspectives. MDMA is associated with unique psychopharmacological effects, including: 1) reduced fear, 2) enhanced wellbeing, 3) increased sociability/extroversion, 4) reduced self-criticism, 5) increased compassion for self/others, 6) increased interpersonal trust, and 7) alert state of consciousness. These anxiolytic and prosocial effects may counteract avoidance and hyperarousal in the context of psychotherapy for those with ED-PTSD. Other clinical features of EDs that may be amenable to MDMA-assisted psychotherapy include body image distortion, cognitive rigidity, and socio-emotional processing difficulties. To illustrate its potential, personal accounts of individuals with ED-PTSD symptoms reporting benefit from MDMA adjunctive to psychotherapy are described. In addition, the possible risks and challenges in conducting this work are addressed, and future implications of this proposal are discussed.

Brewerton, T. D., Lafrance, A., & Mithoefer, M. C. (2021). The potential use of N-methyl-3,4-methylenedioxyamphetamine (MDMA) assisted psychotherapy in the treatment of eating disorders comorbid with PTSD. Medical hypotheses, 146, 110367. https://doi.org/10.1016/j.mehy.2020.110367

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