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Can ecstasy treat the agony of PTSD?

/ Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / /

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

/ Papers, Psychology, Psychotic Disorders, Publications / / , , ,

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

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A systematic review of the effects of novel psychoactive substances 'legal highs' on people with severe mental illness

/ Papers, Psychology, Psychotic Disorders, Publications / / , , ,

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

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Depressant Effects of Salvia divinorum Involve Disruption of Physiological Sleep

/ Papers, Publications, Salvia / Salvinorin A / / , , , , ,

Abstract

Although Salvia divinorum is traditionally known as a ‘mind-altering’ or psychoactive herb used, among others things, as a tranquilizer, this property has not been validated with regard to its efficacy and safety. The objective of this study is to provide evidence for the sedative effects of S. divinorum and discriminate the nature of the responsible constituents by examining different experimental models. A battery of tests, including the open-field, hole-board, exploration cylinder, plus-maze and sodium pentobarbital-induced hypnosis potentiation, were used in mice after administration of non-polar, medium polar and/or polar extracts of the plant (10, 30 and 100 mg/kg). Polysomnographic analysis in rats receiving an active medium polar extract (10 and 100 mg/kg) containing salvinorins was also assessed to study the effects of this plant on sleep architecture. All tested extracts produced significant sedative-like responses, although those of the medium polar extract were more pronounced in mice. The sedative effect of this latter extract, which contains a mixture of salvinorins, caused fragmented sleep architecture in rats by diminishing rapid eye movement (REM) sleep and increased the quiet awake stage at 10 and 100 mg/kg. Our results provide evidence that S. divinorum exhibits sedative-like depressant properties that alter physiological sleep architecture.

González‐Trujano, M. E., Brindis, F., López‐Ruiz, E., Ramírez‐Salado, I., Martínez, A., & Pellicer, F. (2016). Depressant Effects of Salvia divinorum Involve Disruption of Physiological Sleep. Phytotherapy Research. http://dx.doi.org/10.1002/ptr.5617

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Dimethyltryptamine (DMT): a biochemical Swiss Army knife in neuroinflammation and neuroprotection?

/ DMT, Neuroscience, Papers, Publications / / ,

Szabo, A., & Frecska, E. (2016). Dimethyltryptamine (DMT): a biochemical Swiss Army knife in neuroinflammation and neuroprotection?. Neural Regeneration Research, 11(3), 396. http://dx.doi.org/10.4103/1673-5374.179041
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The routes of a plant: ayahuasca and the global networks of Santo Daime

/ Anthropology & Sociology, Ayahuasca, Papers, Publications / / ,

Abstract

This paper examines the Santo Daime religion, the Amazonian town of Céu do Mapiá which is one of its primary spiritual centres, and Ayahuasca, a key sacrament of the Santo Daime religion. The small village in the Amazon demonstrates the active outreach by a place which functions as a nexus of international and intercontinental flows of substances, bodies and meanings. The power of place is entwined with the story of religious belief and practice, which in turn depends on a tropical vine, Banisteriopsis caapi. In this networking process, we find a confluence of human agency with more-than-human agency, as well as the modalities of religious experience, crossing and dwelling. It is demonstrated that religious networking can be understood in terms of three forms of crossing (terrestrial, corporeal and cosmic) held together by the power of place (Mapiá and other subsidiary spiritual centres). In addition, three aspects of the ‘ayahuasca network’ are treated in depth: religious diffusion and adaptation, interaction with environmental movements and ideologies and contestation with legal structures and processes surrounding international drug traffic and the use of psychoactive substances.

Lowell, J. T., & Adams, P. C. (2016). The routes of a plant: ayahuasca and the global networks of Santo Daime. Social & Cultural Geography, 1-21. http://dx.doi.org/10.1080/14649365.2016.1161818
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Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

/ Iboga / Ibogaine, Papers, Publications / / , , , ,

Abstract

Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

Rubi, L., Eckert, D., Boehm, S., Hilber, K., & Koenig, X. (2016). Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Cardiovascular Toxicology, 1-4. http://dx.doi.org/10.1007/s12012-016-9366-y

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Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans

/ Ayahuasca, Neuroscience, Papers, Publications / / , , , , , ,

Abstract

Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans.

Valle, M., Maqueda, A. E., Rabella, M., Rodríguez-Pujadas, A., Antonijoan, R. M., Romero, S., … & Feilding, A. (2016). Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans. European Neuropsychopharmacology. http://dx.doi.org/10.1016/j.euroneuro.2016.03.012

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Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

/ Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / / , , ,

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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Healing culture and its somewhat humorous discontents - July 22

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