Race-Based Trauma: The Challenge and Promise of MDMA-Assisted Psychotherapy
Williams, M. T. Race-Based Trauma: The Challenge and Promise of MDMA-Assisted Psychotherapy.
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Psychology
Can ecstasy treat the agony of PTSD?
Abstract
Two serotonin reuptake inhibitors (SSRIs) have received FDA indication for treatment of PTSD, however the effectiveness of pharmacotherapy for PTSD is limited. Psychotherapy, including several well established evidence based methods, is the mainstay of PTSD treatment. Despite advances in this area, a significant percentage of PTSD patients are refractory to existing treatments. Recent research has explored the possibility that certain drugs could increase the effectiveness of psychotherapy when administered intermittently in conjunction with psychotherapy sessions. The most robust published. Results to date using this approach have been in early clinical trials of±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. These studies primarily involved civilians with treatment-resistant, crime-related PTSD. A more recent phase 2 trial, completed in 2015 yielded equally promising. Results in a cohort of military veterans, police officers and firefighters, mostly veterans from the wars in Iraq and Afghanistan.In these double blind controlled trials subjects with PTSD refractory to prior treatment are randomized to an active dose of MDMA or an active or inactive placebo administered to each individual on only two or three occasions during eight-hour psychotherapy sessions one month apart, in conjunction with preparatory and follow-up psychotherapy sessions. Outcome measures are repeated one or two months after the second MDMA-assisted session before the blind is broken. Subjects who were randomized to full dose MDMA are then eligible for one additional, open label, MDMA-assisted session. Those randomized to placebo or a lower dose of MDMA are eligible for three open-label full dose sessions. Outcome measures are repeated two months following the third MDMA-assisted session. The primary outcome measure is the Clinician Administered PTSD Scale (CAPS). Additional measures include the Beck Depression Inventory-II (BDI-II), Global Assessment of Functioning (GAF), Pittsburgh Sleep Quality Index (PSQI) and Posttraumatic Growth Inventory (PTGI).In the original study comparing MDMA with inactive placebo along with the same psychotherapy PTSD was resolved in 83% of the MDMA group vs. 25% of the placebo group receiving the same therapy. Improvement was maintained for at least 74% of subjects at long-term follow-up a mean of 45 months later. In a more recent, unpublished, study both the high dose and the medium dose of MDMA showed large effect sizes in reducing CAPS scores, and improvements in secondary measures: and BDI-II, PSQI, GAF and PTGI.Evidence in phase II trials suggest that MDMA-assisted psychotherapy is effective in treating PTSD in both civilians and veterans who have not responded to established treatments. Phase III trials are necessary to definitively establish safety and efficacy of MDMA-assisted psychotherapy for PTSD.
Mithoefer, M. (2016). Can ecstasy treat the agony of PTSD?. European Psychiatry, (33), S10. http://dx.doi.org/10.1016%2Fj.eurpsy.2016.01.798
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A systematic review of the effects of novel psychoactive substances ‘legal highs’ on people with severe mental illness
Abstract
WHAT IS KNOWN ON THE SUBJECT?: Novel psychoactive substances (NPS) include synthetic drugs mimicking the effects of illicit drugs, e.g. synthetic cannabinoids, and herbs such as Salvia divinorum. NPS are substances that can trigger hallucinations and other effects altering the mind, and are currently uncontrolled by the United Nations’ 1961 Narcotic Drugs/1971 Psychotropic Substances Conventions. NPS affect brain chemistry that induces the psychoactive effects, such as hallucinations and feeling ‘high’. It is unknown what effects such drugs have on people with severe mental illness (i.e. psychotic illnesses).
WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Our review demonstrates that little is known about the effects of various NPS on people with severe mental illness. Almost nothing is known about the long-term consequences of NPS use on the mental and physical health of SMI patients. Patients may lack understanding that NPS are psychoactive drugs that can impact on their mental and physical wellbeing.
WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Some patients might be reluctant or do not think it is relevant to disclose NPS use. Commonly used illicit drug screening is unlikely to detect the presence of NPS, therefore health and mental health professionals should directly enquire about NPS and actively encourage patients with severe mental illness to disclose any substance use.
PATIENT AND PUBLIC INVOLVEMENT IN THE RESEARCH: There was no significant patient and public involvement in the development and conduct of this study .
ABSTRACT: Introduction Novel psychoactive substances (NPS) are synthetic substances that have been developed to produce altered states of consciousness and perceptions. People with severe mental illness (SMI) are more likely to use NPS than people without mental illness, but the short- and long-term effects of NPS are largely unknown. Method We systematically reviewed the literature about the effects of NPS on people with SMI. Results We included 12 case reports, 1 cross-sectional survey and 1 qualitative study. Participants included mostly males aged between 20 and 35 years. A variety of NPS were used, including synthetic cathinones and herbs such as Salvia. The most commonly reported effects of NPS were psychotic symptoms (in some cases novel in form and content to the patients’ usual symptoms) and significant changes in behaviour, including agitation, aggression and violence. Patients’ vital signs, such as blood pressure, pulse rate and temperature, were also commonly affected.
CONCLUSION: NPS potentially have serious effects on people with SMI, but our findings have limited generalizability due to a reliance on case studies. There is a paucity of evidence about the long-term effects of these substances. Further research is required to provide a better understanding about how different NPS affect patients’ mental and physical health.
Gray, R., Bressington, D., Hughes, E., & Ivanecka, A. (2016). A systematic review of the effects of novel psychoactive substances ‘legal highs’ on people with severe mental illness. Journal of Psychiatric and Mental Health Nursing. http://dx.doi.org/10.1111/jpm.12297
A systematic review of the effects of novel psychoactive substances 'legal highs' on people with severe mental illness
Abstract
WHAT IS KNOWN ON THE SUBJECT?: Novel psychoactive substances (NPS) include synthetic drugs mimicking the effects of illicit drugs, e.g. synthetic cannabinoids, and herbs such as Salvia divinorum. NPS are substances that can trigger hallucinations and other effects altering the mind, and are currently uncontrolled by the United Nations’ 1961 Narcotic Drugs/1971 Psychotropic Substances Conventions. NPS affect brain chemistry that induces the psychoactive effects, such as hallucinations and feeling ‘high’. It is unknown what effects such drugs have on people with severe mental illness (i.e. psychotic illnesses).
WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Our review demonstrates that little is known about the effects of various NPS on people with severe mental illness. Almost nothing is known about the long-term consequences of NPS use on the mental and physical health of SMI patients. Patients may lack understanding that NPS are psychoactive drugs that can impact on their mental and physical wellbeing.
WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Some patients might be reluctant or do not think it is relevant to disclose NPS use. Commonly used illicit drug screening is unlikely to detect the presence of NPS, therefore health and mental health professionals should directly enquire about NPS and actively encourage patients with severe mental illness to disclose any substance use.
PATIENT AND PUBLIC INVOLVEMENT IN THE RESEARCH: There was no significant patient and public involvement in the development and conduct of this study .
ABSTRACT: Introduction Novel psychoactive substances (NPS) are synthetic substances that have been developed to produce altered states of consciousness and perceptions. People with severe mental illness (SMI) are more likely to use NPS than people without mental illness, but the short- and long-term effects of NPS are largely unknown. Method We systematically reviewed the literature about the effects of NPS on people with SMI. Results We included 12 case reports, 1 cross-sectional survey and 1 qualitative study. Participants included mostly males aged between 20 and 35 years. A variety of NPS were used, including synthetic cathinones and herbs such as Salvia. The most commonly reported effects of NPS were psychotic symptoms (in some cases novel in form and content to the patients’ usual symptoms) and significant changes in behaviour, including agitation, aggression and violence. Patients’ vital signs, such as blood pressure, pulse rate and temperature, were also commonly affected.
CONCLUSION: NPS potentially have serious effects on people with SMI, but our findings have limited generalizability due to a reliance on case studies. There is a paucity of evidence about the long-term effects of these substances. Further research is required to provide a better understanding about how different NPS affect patients’ mental and physical health.
Gray, R., Bressington, D., Hughes, E., & Ivanecka, A. (2016). A systematic review of the effects of novel psychoactive substances ‘legal highs’ on people with severe mental illness. Journal of Psychiatric and Mental Health Nursing. http://dx.doi.org/10.1111/jpm.12297
Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies
Abstract
Objective:
To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline).
Methods:
Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection.
Results:
Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression.
Conclusion:
Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.
dos Santos, R. G., Osório, F. L., Crippa, J. A. S., & Hallak, J. E. (2016). Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies. Revista Brasileira de Psiquiatria, 38(1), 65-72. http://dx.doi.org/10.1590/1516-4446-2015-1701
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Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide
Abstract
This paper reports on the effects of LSD on mental time travel during spontaneous mentation. Twenty healthy volunteers participated in a placebo-controlled crossover study, incorporating intravenous administration of LSD (75 μg) and placebo (saline) prior to functional magnetic resonance imaging (fMRI). Six independent, blind judges analysed mentation reports acquired during structured interviews performed shortly after the functional magnetic resonance imaging (fMRI) scans (approximately 2.5 h post-administration). Within each report, specific linguistic references to mental spaces for the past, present and future were identified. Results revealed significantly fewer mental spaces for the past under LSD and this effect correlated with the general intensity of the drug’s subjective effects. No differences in the number of mental spaces for the present or future were observed. Consistent with the previously proposed role of the default-mode network (DMN) in autobiographical memory recollection and ruminative thought, decreased resting-state functional connectivity (RSFC) within the DMN correlated with decreased mental time travel to the past. These results are discussed in relation to potential therapeutic applications of LSD and related psychedelics, e.g. in the treatment of depression, for which excessive reflection on one’s past, likely mediated by DMN functioning, is symptomatic.
Speth, J., Speth, C., Kaelen, M., Schloerscheidt, A. M., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2016). Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide. Journal of psychopharmacology (Oxford, England), 30(4), 344. http://dx.doi.org/10.1177/0269881116628430
Lysergic acid diethylamide: a drug of ‘use’?
Abstract
Lysergic acid diethylamide (LSD), described as a classical hallucinogen, began its journey from the middle of the last century following an accidental discovery. Since then, it was used as a popular and notorious substance of abuse in various parts of the world. Its beneficial role as an adjunct to psychotherapy was much unknown, until some ‘benevolent’ experiments were carried out over time to explore some of its potential uses. But, many of its effects were unclear and seemed to be a psychedelic enigma. In this review article, we have described the receptor pharmacology, mechanism of action, effects and adverse effects of LSD on the normal body system. We have also highlighted its addictive potentials and the chances of developing tolerance. We have assimilated some of the interesting therapeutic uses of this drug, such as an antianxiety agent, a creativity enhancer, a suggestibility enhancer, and a performance enhancer. We have also described LSD to be successfully used in drug and alcohol dependence, and as a part of psychedelic peak therapy in terminally ill patients. The relevant chronological history and literature in the light of present knowledge and scenarios have been discussed. Based on available evidence, LSD could be tried therapeutically in certain specific conditions under controlled settings. But as we mention, due to all the safety concerns, the use of this nonaddictive ‘entheogen’ in actual practice warrants a lot of expertise, caution, cooperation and ethical considerations.
Das, S., Barnwal, P., Ramasamy, A., Sen, S., & Mondal, S. (2016). Lysergic acid diethylamide: a drug of ‘use’?. Therapeutic Advances in Psychopharmacology, 2045125316640440.
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Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years
Abstract
To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer-reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings.
dos Santos, R. G., Osório, F. L., Crippa, J. A. S., Riba, J., Zuardi, A. W., & Hallak, J. E. (2016). Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years. Therapeutic Advances in Psychopharmacology, 2045125316638008.
Effects of 3,4-Methylenedioxymethamphetamine on Patient Utterances in a Psychotherapeutic Setting
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) administered as an adjunct to talk therapy influences patient speech content and increases improvement in treatment-resistant posttraumatic stress disorder (PTSD). Data came from the recordings of Mithoefer et al. (2011). In the third therapeutic session studied, patients were assigned, double blind, to an MDMA or a placebo group. Condition-blind scorers listened to therapy recordings and scored utterances where patients initiated topics that were empathic (regarding others’ emotions), entactic (requesting or appreciating physical touch), or ensuic (describing a change in their sense of themselves). Patients who received MDMA produced high levels of ensuic, empathic, and entactic utterances compared with those who received the placebo. Interrater discourse scoring was reliable. The relationship between the number of scored utterances and the Clinician Administered PTSD Scale scores measuring PTSD severity after the treatment was significant, and reanalysis grouped bimodally into “many” or “few” such utterances remained significant. MDMA assisted these patients in having meaningful and disorder-resolving thoughts and discourse in talk therapy.
Corey, V. R., Pisano, V. D., & Halpern, J. H. (2016). Effects of 3, 4-Methylenedioxymethamphetamine on Patient Utterances in a Psychotherapeutic Setting. The Journal of Nervous and Mental Disease. http://dx.doi.org/10.1097/NMD.0000000000000499
Meta-analysis of executive functioning in ecstasy/polydrug users
Abstract
Ecstasy/3,4-methylenedioxymethamphetamine (MDMA) use is proposed to cause damage to serotonergic (5-HT) axons in humans. Therefore, users should show deficits in cognitive processes that rely on serotonin-rich, prefrontal areas of the brain. However, there is inconsistency in findings to support this hypothesis. The aim of the current study was to examine deficits in executive functioning in ecstasy users compared with controls using meta-analysis. We identified k = 39 studies, contributing 89 effect sizes, investigating executive functioning in ecstasy users and polydrug-using controls. We compared function-specific task performance in 1221 current ecstasy users and 1242 drug-using controls, from tasks tapping the executive functions – updating, switching, inhibition and access to long-term memory. The significant main effect demonstrated overall executive dysfunction in ecstasy users [standardized mean difference (SMD) = -0.18, 95% confidence interval (CI) -0.26 to -0.11, Z = 5.05, p < 0.001, I 2 = 82%], with a significant subgroup effect (χ 2 = 22.06, degrees of freedom = 3, p < 0.001, I 2 = 86.4%) demonstrating differential effects across executive functions. Ecstasy users showed significant performance deficits in access (SMD = -0.33, 95% CI -0.46 to -0.19, Z = 4.72, p < 0.001, I 2 = 74%), switching (SMD = -0.19, 95% CI -0.36 to -0.02, Z = 2.16, p < 0.05, I 2 = 85%) and updating (SMD = -0.26, 95% CI -0.37 to -0.15, Z = 4.49, p < 0.001, I 2 = 82%). No differences were observed in inhibitory control. We conclude that this is the most comprehensive analysis of executive function in ecstasy users to date and provides a behavioural correlate of potential serotonergic neurotoxicity.
Roberts, C. A., Jones, A., & Montgomery, C. (2016). Meta-analysis of executive functioning in ecstasy/polydrug users. Psychological medicine, 1-16. http://dx.doi.org/10.1017/S0033291716000258
