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Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials

May 11, 2020 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Rationale: Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual’s health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD.
Objectives: To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD.
Methods: Participants received two to three active doses of MDMA (75-125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire.
Results: There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = – 44.8 (2.82), p < .0001), with a Cohen’s d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = – 5.2 (2.29), p < .05), with a Cohen’s d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation.
Conclusions: PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD.

Jerome, L., Feduccia, A. A., Wang, J. B., Hamilton, S., Yazar-Klosinski, B., Emerson, A., … & Doblin, R. (2020). Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology., https://doi.org/10.1007/s00213-020-05548-2
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Psychedelic treatment of functional neurological disorder: a systematic review

May 11, 2020 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Functional neurological disorder (FND), formerly known as conversion disorder, causes a high burden of disability and distress, and is amongst the most commonly encountered conditions in neurology clinics and neuropsychiatric services, yet the therapeutic evidence base is somewhat limited. There has been recent interest in the therapeutic potential of psychedelics such as psilocybin and lysergic acid diethylamide (LSD), and in recent studies psychedelics have shown promise in treating a range of neuropsychiatric conditions. Modification of neural circuits associated with self-representation is thought to underlie some of this effect, and as some contemporary theories of FND focus on aberrant somatic self-representation, psychedelics may therefore represent an unexplored treatment option for FND. We systematically reviewed studies involving the use of psychedelics in FND. Nine studies published between 1954 and 1967, with a total of 26 patients, were identified. Due to restriction of licencing of psychedelic drugs since this period, no modern studies were identified. In most cases, patients received a course of psychotherapy with variable adjunctive administration of psychedelics (in a combination known as ‘psycholytic therapy’), with protocols varying between studies. Of those treated, 69% (n = 18) were found to have made at least some recovery on heterogeneous and subjective clinician-rated criteria. Adverse events were mostly mild and transient; however, at least one patient terminated the study due to distressing effects. All included studies were of low quality, often lacking control groups and valid outcome measures. Although no conclusions on efficacy may be drawn from these data, further research may help to determine whether psychedelics offer a feasible, safe and effective treatment for FND.
Butler, M., Seynaeve, M., Nicholson, T. R., Pick, S., Kanaan, R. A., Lees, A., … & Rucker, J. (2020). Psychedelic treatment of functional neurological disorder: a systematic review. Therapeutic Advances in Psychopharmacology, 10, 2045125320912125., https://doi.org/10.1177%2F2045125320912125
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Can Psychedelics Alleviate Symptoms of Cluster Headache and Accompanying Mental Health Problems? A Case Report Involving Hawaiian Baby Woodrose

May 7, 2020 / Depressive Disorders, Papers, Psychology, Publications / By / ,

Abstract

Preliminary evidence supports the efficacy of psychedelics in the alleviation of cluster headache and mental health problems. We describe a case of an individual with cluster headache and mood disorder who claims to have benefited from her use of psychedelics. A forty-eight-year-old woman was referred to a private Australian mental health clinic for the management of chronic pain and depression. She reported using Hawaiian baby woodrose to successfully alleviate symptoms of cluster headache and the accompanying mental health problems. Incidental observation also highlighted the potential therapeutic benefits of antiviral therapy. This is the first case report to concurrently examine the analgesic and psycho-spiritual effects of Hawaiian baby woodrose, with results in support of nascent research in this field. The results of this case report highlight the need for further research into the use of psychedelics in the management of cluster headache and mental illness
Johnson, S., & Black, Q. C. (2020). Can Psychedelics Alleviate Symptoms of Cluster Headache and Accompanying Mental Health Problems? A Case Report Involving Hawaiian Baby Woodrose. Journal of Psychoactive Drugs, 1-5., https://doi.org/10.1080/02791072.2020.1762023
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Psilocybin and LSD Have No Long-Lasting Effects in an Animal Model of Alcohol Relapse

May 5, 2020 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , ,

Abstract

For most psychiatric disorders, including alcohol use disorder (AUD), approved pharmacological treatments are limited in their effectiveness, and new drugs that can easily be translated into the clinic are needed. Currently, great hope lies in the potential of psychedelics to effectively treat AUD. The primary hypothesis is that a single session of psychedelic-guided psychotherapy can restore normal brain function in AUD individuals and thereby reduce the risk of relapse in the long run. Here we applied three different treatment schedules with psilocybin/LSD in order to investigate relapse-like drinking in the alcohol deprivation effect (ADE) model. In contrast to the primary hypothesis, psychedelics had no long-lasting effects on the ADE in male and female rats, neither when administered in a high dosage regime that is comparable to the one used in clinical studies, nor in a chronic microdosing scheme. Only sub-chronic treatment with psilocybin produced a short-lasting anti-relapse effect. However, it is not a translatable treatment option to give psychedelics sub-chronically for relapse prevention. In conclusion, our results in the ADE model do not support the hypothesis that microdosing or high doses of psychedelic reduce relapse behavior. This conclusion has to be confirmed by applying other animal models of AUD. It could also well be that animal models of AUD might be unable to fully capture the therapeutic potential of psychedelic drugs and that only future large-scale clinical trials will be able to demonstrate the efficacy of psychedelics as a new treatment option for AUD.

Meinhardt, M. W., Güngör, C., Skorodumov, I., Mertens, L. J., & Spanagel, R. (2020). Psilocybin and LSD have no long-lasting effects in an animal model of alcohol relapse. Neuropsychopharmacology, 1-9., https://doi.org/10.1038/s41386-020-0694-z
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Chronic pain and psychedelics: a review and proposed mechanism of action

May 4, 2020 / Ayahuasca, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

The development of chronic pain is a complex mechanism that is still not fully understood. Multiple somatic and visceral afferent pain signals, when experienced over time, cause a strengthening of certain neural circuitry through peripheral and central sensitization, resulting in the physical and emotional perceptual chronic pain experience. The mind-altering qualities of psychedelics have been attributed, through serotonin 2A (5-HT2A) receptor agonism, to ‘reset’ areas of functional connectivity (FC) in the brain that play prominent roles in many central neuropathic states. Psychedelic substances have a generally favorable safety profile, especially when compared with opioid analgesics. Clinical evidence to date for their use for chronic pain is limited; however, several studies and reports over the past 50 years have shown potential analgesic benefit in cancer pain, phantom limb pain and cluster headache. While the mechanisms by which the classic psychedelics may provide analgesia are not clear, several possibilities exist given the similarity between 5-HT2A activation pathways of psychedelics and the nociceptive modulation pathways in humans. Additionally, the alterations in FC seen with psychedelic use suggest a way that these agents could help reverse the changes in neural connections seen in chronic pain states. Given the current state of the opioid epidemic and limited efficacy of non-opioid analgesics, it is time to consider further research on psychedelics as analgesics in order to improve the lives of patients with chronic pain conditions.
Castellanos, J. P., Woolley, C., Bruno, K. A., Zeidan, F., Halberstadt, A., & Furnish, T. (2020). Chronic pain and psychedelics: a review and proposed mechanism of action. Regional Anesthesia & Pain Medicine., http://dx.doi.org/10.1136/rapm-2020-101273
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The Viability of Microdosing Psychedelics as a Strategy to Enhance Cognition and Well-being – An Early Review

May 2, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Psychedelic substances are currently experiencing a renaissance in interest for both therapeutic as well as recreational applications. It has been proposed that microdosing, i.e., ingesting sub-perceptual doses of a psychedelic, could confer some of the benefits of these substances to users while minimizing the risks associated with full-dose use. This review aimed to summarize and examine the extant literature on psychedelic microdosing. Exploratory evidence published to date indicates a variety of benefits reported by microdosers including improvements in mood, focus, and creativity, with some null reports, and a minority of people reporting selective negative consequences such as increased anxiety and physiological discomfort. Methodological limitations of current evidence, however, make definitive conclusions hard to draw. Recommendations for future research are given.
Bornemann, J. (2020). The Viability of Microdosing Psychedelics as a Strategy to Enhance Cognition and Well-being-An Early Review. Journal of Psychoactive Drugs, 1-9., https://doi.org/10.1080/02791072.2020.1761573
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Psychedelics and Psychedelic-Assisted Psychotherapy

May 1, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

Objective: The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders.
Methods: Searches of PubMed and PsycINFO via Ovid were conducted for articles in English, in peer-reviewed journals, reporting on “psilocybin,” “lysergic acid diethylamide,” “LSD,” “ayahuasca,” “3,4-methylenedioxymethamphetamine,” and “MDMA,” in human subjects, published between 2007 and July 1, 2019. A total of 1,603 articles were identified and screened. Articles that did not contain the terms “clinical trial,” “therapy,” or “imaging” in the title or abstract were filtered out. The 161 remaining articles were reviewed by two or more authors. The authors identified 14 articles reporting on well-designed clinical trials investigating the efficacy of lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and ayahuasca for the treatment of mood and anxiety disorders, trauma and stress-related disorders, and substance-related and addictive disorders as well as in end-of-life care.
Results: The most significant database exists for MDMA and psilocybin, which have been designated by the U.S. Food and Drug Administration (FDA) as “breakthrough therapies” for posttraumatic stress disorder (PTSD) and treatment-resistant depression, respectively. The research on LSD and ayahuasca is observational, but available evidence suggests that these agents may have therapeutic effects in specific psychiatric disorders.
Conclusions: Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin in the treatment of depression and cancer-related anxiety. The research to support the use of LSD and ayahuasca in the treatment of psychiatric disorders is preliminary, although promising. Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.

Keywords: Ayahuasca; Drug-Psychotherapy Combination; Lysergic Acid Diethylamide; MDMA; Psilocybin; Psychedelics.
Reiff, C. M., Richman, E. E., Nemeroff, C. B., Carpenter, L. L., Widge, A. S., Rodriguez, C. I., … & Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of Research. (2020). Psychedelics and psychedelic-assisted psychotherapy. American Journal of Psychiatry, 177(5), 391-410., https://doi.org/10.1176/appi.ajp.2019.19010035
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Ayahuasca – potential therapeutic properties in psychiatry. Research review

April 30, 2020 / Ayahuasca, DMT, Papers, Psychology, Publications / By / ,

Abstract

Ayahuasca, also known as “the liana of the soul” and “the vine of the soul” is a ritual psychedelic traditionally administered in the form of plant decoction, used by the indigenous people of South America for centuries, and in the last 25 years also in Europe, Asia, Africa, Australia, Canada, and the United States. Its biological activity results from the content of N,N-dimethyltryptamine (DMT), acting mainly as a non-selective agonist of serotonin receptors and beta-carboline alkaloids, which are strong and short-acting monoamine oxidase type A(MAOI-A) inhibitors. For many years there have been reports of both the anti-anxiety and antidepressant effects of ayahuasca, as well as indications of the possibility of its use in the treatment of addictions. The results of studies of its effectiveness in drug-resistant depression seem to be promising, comparable in the opinion of some authors with the effect of therapeutic action of ketamine. In the article, we try to explain the complex profile of action and the resulting potential benefits, but also the risk of interaction and adverse effects associated with the taking of ayahuasca, which is important given the high variability of herbal mixtures used to produce the decoction.

Barabasz-Gembczyk, A., & Kucia, K. (2020). Ayahuasca–potential therapeutic properties in psychiatry. Research review. Psychiatr. Pol.. Pol, 54(2), 381-389., https://doi.org/10.12740/PP/103364
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Stability Evaluation of DMT and Harmala Alkaloids in Ayahuasca Tea Samples

February 6, 2022 / Ayahuasca, Papers, Pharmacology & Chemistry / Leave a Comment / By / , , , , ,

Abstract

Ayahuasca tea is a hallucinogenic beverage used for religious purposes in Brazil and many other countries that has therapeutic potential in the treatment of some mental health disorders. In the context of psychedelic research, quantification of the tea’s main alkaloids prior to its administration in animal or human studies is essential. For this reason, this study aims to provide information regarding the stability of the main ayahuasca alkaloids (dimethyltryptamine, DMT; harmine, HRM; tetrahydroharmine, THH; harmaline, HRL) in three different conditions: (1) A year stored in a refrigerator either in plastic or glass containers, (2) seven days at 37 °C to reproduce usual mail transportation, and (3) after three freeze-thaw cycles. Samples were quantified after a dilute-and-shoot procedure using liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). There was no significant degradation of DMT concentration over time in all tested conditions. Harmala alkaloids (THH, HRL, and HRM) showed important variations after long-term and high-temperature storages. Although DMT has proven to be stable in all studied conditions, the harmala alkaloids revealed intense degradation and even concentration increment. This may be caused by degradation, alkaloid inter-conversion, and leaching from tea precipitate material. Therefore, ayahuasca quantification before administration in controlled sets is mandatory.

de Oliveira Silveira, G., Guimarães Dos Santos, R., Rebello Lourenço, F., Novak Rossi, G., Hallak, J., & Yonamine, M. (2020). Stability Evaluation of DMT and Harmala Alkaloids in Ayahuasca Tea Samples. Molecules (Basel, Switzerland), 25(9), 2072. https://doi.org/10.3390/molecules25092072

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A Single Administration of the Atypical Psychedelic Ibogaine or Its Metabolite Noribogaine Induces an Antidepressant-Like Effect in Rats

April 24, 2020 / Depressive Disorders, Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , , ,

Abstract

Anecdotal reports and open-label case studies in humans indicated that the psychedelic alkaloid ibogaine exerts profound antiaddictive effects. Ample preclinical evidence demonstrated the efficacy of ibogaine, and its main metabolite, noribogaine, in substance-use-disorder rodent models. In contrast to addiction research, depression-relevant effects of ibogaine or noribogaine in rodents have not been previously examined. We have recently reported that the acute ibogaine administration induced a long-term increase of brain-derived neurotrophic factor mRNA levels in the rat prefrontal cortex, which led us to hypothesize that ibogaine may elicit antidepressant-like effects in rats. Accordingly, we characterized behavioral effects (dose- and time-dependence) induced by the acute ibogaine and noribogaine administration in rats using the forced swim test (FST, 20 and 40 mg/kg i.p., single injection for each dose). We also examined the correlation between plasma and brain concentrations of ibogaine and noribogaine and the elicited behavioral response. We found that ibogaine and noribogaine induced a dose- and time-dependent antidepressant-like effect without significant changes of animal locomotor activity. Noribogaine’s FST effect was short-lived (30 min) and correlated with high brain concentrations (estimated >8 μM of free drug), while the ibogaine’s antidepressant-like effect was significant at 3 h. At this time point, both ibogaine and noribogaine were present in rat brain at concentrations that cannot produce the same behavioral outcome on their own (ibogaine ∼0.5 μM, noribogaine ∼2.5 μM). Our data suggests a polypharmacological mechanism underpinning the antidepressant-like effects of ibogaine and noribogaine.
Rodríguez, P., Urbanavicius, J., Prieto, J. P., Fabius, S., Reyes, A. L., Havel, V., … & Carrera, I. (2020). A Single Administration of the Atypical Psychedelic Ibogaine or its Metabolite Noribogaine Induces an Antidepressant-like Effect in Rats. ACS Chemical Neuroscience., https://doi.org/10.1021/acschemneuro.0c00152
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