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Anxiety Disorders / PTSD

How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review.

January 31, 2019 / Anxiety Disorders / PTSD, Papers, Psychology, Psychotic Disorders, Publications, Substance Use Disorder / By / , , , , ,

Abstract

We conducted a review of systematic reviews (SRs) and randomized-controlled trials (RCTs) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders. Five data bases were systematically searched (2006-August 2018); 4 SRs (of 11 RCTs) and 14 RCTs (1629 participants) were included. Diagnoses were: dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette`s disorder. Outcome variables were too heterogeneous to conduct a  meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists. THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.
Hoch, E., Niemann, D., von Keller, R., Schneider, M., Friemel, C. M., Preuss, U. W., … & Pogarell, O. (2019). How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review. European archives of psychiatry and clinical neuroscience, 269(1), 87-105., https://doi.org/10.1007/s00406-019-00984-4
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Perceived Benefits of MDMA-Assisted Psychotherapy beyond Symptom Reduction: Qualitative Follow-Up Study of a Clinical Trial for Individuals with Treatment-Resistant PTSD.

January 7, 2019 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

We present select findings from a long-term follow-up qualitative study of MDMA-assisted psychotherapy for veterans, firefighters, and police officers suffering from chronic, treatment-resistant PTSD. Semi-structured qualitative interviews were conducted at participants’ one-year follow-up after a recently completed phase 2 clinical trial. Available interviews from 19 of 24 participants were analyzed. This qualitative analysis sought to complement, clarify, and expand upon the quantitative findings obtained from the Clinician Administered PTSD Scale (CAPS-IV) and supported by the Long-Term Follow-Up (LTFU) Questionnaire. Pertinent data from interview transcripts were coded and analyzed using an interpretative phenomenological analysis (IPA) methodological framework. We explore prominent thematic elements from participant accounts to better understand the outcomes experienced in this trial. All participants reported experiencing lasting personal benefits and enhanced quality of life that extend beyond quantifiable symptom reduction. We explore a range of treatment benefits beyond symptom reduction to highlight the utility of qualitative investigations of the process and effects of MDMA-assisted psychotherapy. Limitations and challenges encountered in conducting this study are discussed along with recommendations for improved qualitative research protocols in future clinical trials.
Barone, W., Beck, J., Mitsunaga-Whitten, M., & Perl, P. (2019). Perceived Benefits of MDMA-Assisted Psychotherapy beyond Symptom Reduction: Qualitative Follow-Up Study of a Clinical Trial for Individuals with Treatment-Resistant PTSD. Journal of psychoactive drugs, 1-10., https://doi.org/10.1080/02791072.2019.1580805
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The effects of ketamine on suicidality across various formulations and study settings

January 4, 2019 / Anxiety Disorders / PTSD, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By / ,

Abstract

INTRODUCTION:

Suicidality and self-injurious behavior afflict patients with a wide variety of psychiatric illnesses. Currently, there are few pharmacologic treatments for suicidality and self-injurious behavior and none that treat these conditions emergently. Recently, ketamine has demonstrated efficacy in treating both depression and acute suicidal ideation. An increasing usage of ketamine, of a variety of formulations, has been studied for these indications. This article reviews the evidence for use of ketamine in self-injurious behavior and suicidality.

METHODS:

A review of the MEDLINE database for articles relating to ketamine, self-injurious behavior, suicidality, and self-harm was conducted. Additional articles were assessed via cross-reference.

RESULTS:

A total of 24 articles that included clinical trials, meta-analyses, case series, and case reports were analyzed. The majority of studies of ketamine for suicidal ideation include the intravenous route using a dose of 0.5 mg/kg over 40 minutes. These studies suggest that intravenous ketamine may be effective at reducing suicidal ideation acutely. Data on use of ketamine in the intramuscular, intranasal, and oral forms are limited and of poorer quality. Studies on these formulations contain greater variability of positive and negative results of ketamine for reducing suicidality and self-injurious behavior. The durability of the antisuicidal effects across all formulations is limited.

DISCUSSION:

Ketamine may be an effective option for the treatment of suicidal ideation in patients across inpatient, outpatient, or emergent settings. At this time, more research is needed on the efficacy of ketamine across all formulations being used in clinical practice.

Dadiomov, D., & Lee, K. (2019). The effects of ketamine on suicidality across various formulations and study settings. Mental Health Clinician, 9(1), 48-60., 10.9740/mhc.2019.01.048
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Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment‐resistant depression

December 30, 2018 / Anxiety Disorders / PTSD, Ketamine, Papers, Publications / By / , , , , , ,

Abstract

Objective

To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment‐resistant depression (TRD).

Methods

In a multisite, double‐blind, placebo‐controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure was changed in the six‐item Hamilton Rating Scale for Depression (HAMD6). A linear mixed effects model was used to examine the effect of anxious depression baseline status (defined by a Hamilton Depression Rating Scale Anxiety‐Somatization score ≥7) on response to ketamine versus midazolam at 1 and 3 days postinfusion.

Results

N = 45 subjects had anxious TRD, compared to N = 54 subjects without high anxiety at baseline. No statistically significant interaction effect was found between treatment group assignment (combined ketamine treatment groups versus midazolam) and anxious/nonanxious status on HAMD6 score at either days 1 or 3 postinfusion (Day 1: F(1, 84) = 0.02, P = 0.88; Day 3: F(1, 82) = 0.12, P = 0.73).

Conclusion

In contrast with what is observed with traditional antidepressants, response to ketamine may be similar in both anxious and nonanxious TRD subjects. These pilot results suggest the potential utility of ketamine in the treatment of anxious TRD.

Salloum, N. C., Fava, M., Freeman, M. P., Flynn, M., Hoeppner, B., Hock, R. S., … & Mathew, S. J. (2018). Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment‐resistant depression. Depression and anxiety., 10.1002/da.22875
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Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions.

December 12, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

BACKGROUND:
For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via prosocial effects, increases the ability of patients to address the underlying psychopathology of the disorder. However, the use of MDMA poses potential problems of neurotoxicity, in addition to its own potential for misuse.
METHODS:
In this article, the proposed potential of MDMA as an adjunct to psychotherapy for PTSD is evaluated. The rationale for the use of MDMA and the positive results of studies that have administered MDMA in the treatment of PTSD are provided (pros). A description of potential adverse effects of treatment is also presented (cons). An overview of MDMA pharmacology and pharmacokinetics and a description of potential adverse effects of treatments are also presented. Methylenedioxymethamphetamine-produced oxytocin release and decreased expression of fear conditioning as well as one of the MDMA enantiomers (the n R- entaniomer) are suggested as potential mechanisms for the beneficial effects of MDMA in PTSD (suggestions).
RESULTS:
There is some evidence that MDMA facilitates recovery of PTSD. However, the significant adverse effects of MDMA raise concern for its adoption as a pharmacotherapy. Alternative potential treatments with less adverse effects and that are based on the ubiquitous pharmacology of MDMA are presented.
CONCLUSIONS:
We suggest that additional research investigating the basis for the putative beneficial effects of MDMA might reveal an effective treatment with fewer adverse effects. Suggestions of alternative treatments based on the behavioral pharmacology and toxicology of MDMA and its enantiomers are presented.
Schenk, S., & Newcombe, D. (2018). Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology, 38(6), 632-638., 10.1097/JCP.0000000000000962
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3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats

December 4, 2018 / Anxiety Disorders / PTSD, MDMA, Psychology, Publications / By / , , , , , ,

Abstract

Clinical trials have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) paired with psychotherapy is more effective at reducing symptoms of post-traumatic stress disorder(PTSD) than psychotherapy or pharmacotherapy, alone or in combination. The processes through which MDMA acts to enhance psychotherapy are not well understood. Given that fear memories contribute to PTSD symptomology, MDMA could augment psychotherapy by targeting fear memories. The current studies investigated the effects of a single administration of MDMA on extinction and reconsolidation of cued and contextual fear memory in adult, male Long-Evans rats. Rats were exposed to contextual or auditory fear conditioning followed by systemic administration of saline or varying doses of MDMA (between 1 and 10 mg/kg) either 30 min before fear extinction training or immediately after brief fear memory retrieval (i.e. during the reconsolidation phase). MDMA administered prior to fear extinction training failed to enhance fear extinction memory, and in fact impaired drug-free cued fear extinction recall without impacting later fear relapse. MDMA administered during the reconsolidation phase, but not outside of the reconsolidation phase, produced a delayed and persistent reduction in conditioned fear. These findings are consistent with a general memory-disrupting effect of MDMA and suggest that MDMA could augment psychotherapy by modifying fear memories during reconsolidation without necessarily enhancing their extinction.

Hake, H. S., Davis, J. K., Wood, R. R., Tanner, M. K., Loetz, E. C., Sanchez, A., … & Greenwood, B. N. (2019). 3, 4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats. Physiology & behavior, 199, 343-350., 10.1016/j.physbeh.2018.12.007
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Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics

September 10, 2024 / Anxiety Disorders / PTSD, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Scienitific Discipline / By / , , ,

Abstract

The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are 5HT2AR agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of molecular neuroscience. Promising results were reported for treatment of both end-of-life psychological distress and addiction, and classic psychedelics served as tools for studying the neurobiological bases of psychological disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their association with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We review recent therapeutic studies suggesting efficacy in treating psychological distress associated with life-threatening diseases, treating depression, and treating nicotine and alcohol addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic psychedelic-occasioned mystical experiences are associated with improved psychological outcomes in both healthy volunteer and patient populations. We also review neuroimaging studies that suggest neurobiological mechanisms of psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness. Finally, we provide the most comprehensive review of epidemiological studies of classic psychedelics to date. Notable among these are a number of studies which have suggested the possibility that nonmedical naturalistic (non-laboratory) use of classic psychedelics is associated with positive mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for experimentally investigating mystical experiences and behavioral-brain function more generally.

Johnson, M. W., Hendricks, P. S., Barrett, F. S., & Griffiths, R. R. (2018). Classic Psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics. Pharmacology & therapeutics., 10.1016/j.pharmthera.2018.11.010

 
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Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions.

December 1, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

BACKGROUND:
For a number of mental health disorders, including posttraumatic stress disorders (PTSD), there are not many available treatment options. Recently, there has been renewed interest in the potential of methylenedioxymethamphetamine (MDMA) to restore function for patients with these disorders. The primary hypothesis is that MDMA, via prosocial effects, increases the ability of patients to address the underlying psychopathology of the disorder. However, the use of MDMA poses potential problems of neurotoxicity, in addition to its own potential for misuse.
METHODS:
In this article, the proposed potential of MDMA as an adjunct to psychotherapy for PTSD is evaluated. The rationale for the use of MDMA and the positive results of studies that have administered MDMA in the treatment of PTSD are provided (pros). A description of potential adverse effects of treatment is also presented (cons). An overview of MDMA pharmacology and pharmacokinetics and a description of potential adverse effects of treatments are also presented. Methylenedioxymethamphetamine-produced oxytocin release and decreased expression of fear conditioning as well as one of the MDMA enantiomers (the n R- entaniomer) are suggested as potential mechanisms for the beneficial effects of MDMA in PTSD (suggestions).
RESULTS:
There is some evidence that MDMA facilitates recovery of PTSD. However, the significant adverse effects of MDMA raise concern for its adoption as a pharmacotherapy. Alternative potential treatments with less adverse effects and that are based on the ubiquitous pharmacology of MDMA are presented.
CONCLUSIONS:
We suggest that additional research investigating the basis for the putative beneficial effects of MDMA might reveal an effective treatment with fewer adverse effects. Suggestions of alternative treatments based on the behavioral pharmacology and toxicology of MDMA and its enantiomers are presented.
Schenk, S., & Newcombe, D. (2018). Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. Journal of clinical psychopharmacology, 38(6), 632-638., 10.1097/JCP.0000000000000962
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An exploratory study of experiences with conventional eating disorder treatment and ceremonial ayahuasca for the healing of eating disorders

September 10, 2024 / Anxiety Disorders / PTSD, Ayahuasca, Papers, Psychology, Publications, Scienitific Discipline / By / , , , , ,

Abstract

Purpose

Ayahuasca is a traditional Amazonian medicine that is currently being researched for its potential in treating a variety of mental disorders. This article reports on exploratory qualitative research relating to participant experiences with ceremonial ayahuasca drinking and conventional treatment for eating disorders (EDs). It also explores the potential for ayahuasca as an adjunctive ED treatment.

Methods

Thirteen individuals previously diagnosed with an ED participated in a semi-structured interview contrasting their experiences with conventional ED treatment with experiences from ceremonial ayahuasca. The interviews were analyzed using thematic analysis.

Results

Participant reports were organized with key themes including that ayahuasca: led to rapid reductions in ED thoughts and symptoms; allowed for the healing of the perceived root of the ED; helped to process painful feelings and memories; supported the internalization of greater self-love and self-acceptance; and catalyzed spiritual elements of healing.

Conclusions

The results suggest that ayahuasca may have potential as a valuable therapeutic tool, and further research—including carefully controlled clinical trials—is warranted.

Renelli, M., Fletcher, J., Tupper, K. W., Files, N., Loizaga-Velder, A., & Lafrance, A. (2018). An exploratory study of experiences with conventional eating disorder treatment and ceremonial ayahuasca for the healing of eating disorders. Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity, 1-8., 10.1007/s40519-018-0619-6
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3,4-Methylenedioxymethamphetamineassisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial

October 29, 2018 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Background:

Posttraumatic stress disorder often does not resolve after conventional psychotherapies or pharmacotherapies. Pilot studies have reported that 3,4-methylenedioxymethamphetamine (MDMA) combined with psychotherapy reduces posttraumatic stress disorder symptoms.

Aims:

This pilot dose response trial assessed efficacy and safety of MDMA-assisted psychotherapy across multiple therapy teams.

Methods:

Twenty-eight people with chronic posttraumatic stress disorder were randomized in a double-blind dose response comparison of two active doses (100 and 125 mg) with a low dose (40 mg) of MDMA administered during eight-hour psychotherapy sessions. Change in the Clinician-Administered PTSD Scale total scores one month after two sessions of MDMA served as the primary outcome. Active dose groups had one additional open-label session; the low dose group crossed over for three open-label active dose sessions. A 12-month follow-up assessment occurred after the final MDMA session.

Results:

In the intent-to-treat set, the active groups had the largest reduction in Clinician-Administered PTSD Scale total scores at the primary endpoint, with mean (standard deviation) changes of −26.3 (29.5) for 125 mg, −24.4 (24.2) for 100 mg, and −11.5 (21.2) for 40 mg, though statistical significance was reached only in the per protocol set (p=0.03). Posttraumatic stress disorder symptoms remained lower than baseline at 12-month follow-up (p<0.001) with 76% (n=25) not meeting posttraumatic stress disorder criteria. There were no drug-related serious adverse events, and the treatment was well-tolerated.

Conclusions:

Our findings support previous investigations of MDMA-assisted psychotherapy as an innovative, efficacious treatment for posttraumatic stress disorder.
Ot’alora G, M., Grigsby, J., Poulter, B., Van Derveer III, J. W., Giron, S. G., Jerome, L., … & Mithoefer, M. C. (2018). 3, 4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial. Journal of Psychopharmacology, 32(12), 1295-1307, https://doi.org/10.1177%2F0269881118806297
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