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Psychiatry

Integrating Psychedelic Medicines and Psychiatry: Theory and Methods of a Model Clinic

Abstract

The past two decades has seen a significant increase in both popular and scientific interest in psychedelic substances and plants as therapeutics for mental illness, addictions, and psychospiritual suffering. Current psychiatric practice privileges a biological paradigm in which the brain is considered the locus of mental illness and symptom-focused treatments are delivered to patients as passive recipients. In contrast, a psychedelic healing paradigm, constructed through examination of different ontologic understandings of plant medicines, is based on a complex multidimensional perspective of human beings and their suffering. This paradigm actively engages the sufferer in addressing root causes of illness through healing on multiple levels of existence, including spiritual and energetic domains. Numerous theoretical, methodological, and ethical challenges complicate the integration of the psychedelic healing paradigm into psychiatric practice. These include developing coherent therapeutic narratives that account for the complex processes by which psychedelic healing occurs and overcoming reductionist tendencies in the medical sciences. Tasked with overcoming such challenges, a model clinic is proposed that seeks to implement and study the psychedelic healing paradigm in a critical, interdisciplinary, and reflexive manner. Such “critical paradigm integration” would employ multimodal patient formulation and treatments, as well as a range of knowledge generation and sharing practices. Outcomes-oriented research would seek to establish an evidence base for the model, while critical dialogues would advance understandings of psychedelic substances and plants and related practices more generally. The clinic would serve as proof of concept for a new model of studying, conceptualizing, and treating mental illness.

Sloshower, J. (2018). Integrating Psychedelic Medicines and Psychiatry: Theory and Methods of a Model Clinic. Plant Medicines, Healing and Psychedelic Science: Cultural Perspectives, 113-132. 10.1007/978-3-319-76720-8_7
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Placebo Problems: Boundary Work in the Psychedelic Science Renaissance

Abstract

The revitalization of clinical trials with psychedelics has produced an array of studies investigating different combinations of therapeutic substances and diagnoses. In addition to the bureaucratic negotiations to gain approval for this research, this new wave of studies is also negotiating a new methodological landscape of clinical research. Mid-twentieth century research with drugs like LSD and psilocybin involved both case studies and double-blind studies. However, today, placebo-controlled randomized controlled trials (RCTs) are the institutional standard for research with psychopharmaceuticals. Because psychedelic therapy seeks to induce a radical change in consciousness—to make a subject feel different from her everyday self—blinding these studies using placebo controls has emerged as a methodological sticking point. However, this chapter argues, it is also a rich site for interrogating boundary work around science and psychedelics. While anthropologists have examined placebos as examples of the power of symbolic healing within Western medicine, or as ethically fraught territory of nontreatment, this chapter examines placebos as a research technique around which the scientific status of a study is negotiated. While psychedelic therapy challenges the model of pharmaceutical intervention used in psychiatry today, it must do so while also working within psychopharmacology’s evidentiary norms.

Hendy, K. (2018). Placebo Problems: Boundary Work in the Psychedelic Science Renaissance. Plant Medicines, Healing and Psychedelic Science: Cultural Perspectives, 151-166. 10.1007/978-3-319-76720-8_9
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Assessment of Alcohol and Tobacco Use Disorders Among Religious Users of Ayahuasca.

Abstract

The aims of this study were to assess the impact of ceremonial use of ayahuasca-a psychedelic brew containing N,N-dimethyltryptamine (DMT) and β-carboline -and attendance at União do Vegetal (UDV) meetings on substance abuse; here we report the findings related to alcohol and tobacco use disorder. A total of 1,947 members of UDV 18+ years old were evaluated in terms of years of membership and ceremonial attendance during the previous 12 months. Participants were recruited from 10 states from all major regions of Brazil. Alcohol and tobacco use was evaluated through questionnaires first developed by the World Health Organization and the Substance Abuse and Mental Health Services Administration. Analyses compared levels of alcohol and tobacco use disorder between the UDV and a national normative sample (n = 7,939). Binomial tests for proportions indicated that lifetime use of alcohol and tobacco was higher in UDV sample compared to the Brazilian norms for age ranges of 25-34 and over 34 years old, but not for the age range of 18-24 years old. However, current use disorders for alcohol and tobacco were significantly lower in the UDV sample than the Brazilian norms. Regression analyses revealed a significant impact of attendance at ayahuasca ceremonies during the previous 12 months and years of UDV membership on the reduction of alcohol and tobacco use disorder.
Ribeiro Barbosa, P. C., Tofoli, L. F., Bogenschutz, M. P., Hoy, R., Berro, L. F., Marinho, E. A., … & Winkelman, M. J. (2018). Assessment of alcohol and tobacco use disorders among religious users of ayahuasca. Frontiers in psychiatry9, 136., 10.3389/fpsyt.2018.00136
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Effects of N, N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression

Abstract

Depression and anxiety disorders are debilitating diseases resulting in substantial economic costs to society. Traditional antidepressants often take weeks to months to positively affect mood and are ineffective for about 30% of the population. Alternatives, such as ketamine, a dissociative anesthetic capable of producing hallucinations, and the psychoactive tisane ayahuasca, have shown great promise due to their fast-acting nature and effectiveness in treatment-resistant populations. Here, we investigate the effects of N, N-dimethyltryptamine (DMT), the principle hallucinogenic component of ayahuasca, in rodent behavioral assays relevant to anxiety and depression using adult, male, Sprague-Dawley rats. We find that while DMT elicits initial anxiogenic responses in several of these paradigms, its long-lasting effects tend to reduce anxiety by facilitating the extinction of cued fear memory. Furthermore, DMT reduces immobility in the forced swim test, which is a characteristic behavioral response induced by many antidepressants. Our results demonstrate that DMT produces antidepressant and anxiolytic behavioral effects in rodents, warranting further investigation of ayahuasca and classical psychedelics as treatments for depression and post-traumatic stress disorder.
Cameron, L. P., Benson, C. J., Dunlap, L. E., & Olson, D. E. (2018). Effects of N, N-dimethyltryptamine on rat behaviors relevant to anxiety and depression. ACS chemical neuroscience. 10.1021/acschemneuro.8b00134
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The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985)

3,4-Methylenedioxymethamphetamine (MDMA), also known as ecstasy, was first synthesized in 1912 but first reached widespread popularity as a legal alternative after the much sought-after recreational drug 3,4-methylenedioxy-amphetamine (MDA) was made illegal in 1970. Because of its benign, feeling-enhancing, and nonhallucinatory properties, MDMA was used by a few dozen psychotherapists in the United States between 1977 and 1985, when it was still legal. This article looks into the contexts and practices of its psychotherapeutic use during these years. Some of the guidelines, recommendations, and precautions developed then are similar to those that apply to psychedelic drugs, but others are specific for MDMA. It is evident from this review that the therapists pioneering the use of MDMA were able to develop techniques (and indications/counterindications) for individual and group therapy that laid the groundwork for the use of MDMA in later scientific studies. In retrospect, it appears that the perceived beneficial effects of MDMA supported a revival of psycholytic/psychedelic therapy on an international scale.
Passie, T. (2018). The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985). Drug Science, Policy and Law4, 2050324518767442., 10.1177/2050324518767442
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Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process

Abstract

Ayahuasca ingestion modulates brain activity, neurotransmission, gene expression and epigenetic regulation. N,N-Dimethyltryptamine (DMT, one of the alkaloids in Ayahuasca) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation. Simultaneously, monoamine oxidase inhibitors (MAOIs) also present in Ayahuasca prevent the degradation of DMT. One peculiarity of SIGMAR1 activation and MAOI activity is the reversal of mnemonic deficits in pre-clinical models. Since traumatic memories in post-traumatic stress disorder (PTSD) are often characterised by “repression” and PTSD patients ingesting Ayahuasca report the retrieval of such memories, it cannot be excluded that DMT-mediated SIGMAR1 activation and the concomitant MAOIs effects during Ayahuasca ingestion might mediate such “anti-amnesic” process. Here I hypothesise that Ayahuasca, via hyperactivation of trauma and emotional memory-related centres, and via its concomitant SIGMAR1- and MAOIs- induced anti-amnesic effects, facilitates the retrieval of traumatic memories, in turn making them labile (destabilised). As Ayahuasca alkaloids enhance synaptic plasticity, increase neurogenesis and boost dopaminergic neurotransmission, and those processes are involved in memory reconsolidation and fear extinction, the fear response triggered by the memory can be reprogramed and/or extinguished. Subsequently, the memory is stored with this updated significance. To date, it is unclear if new memories replace, co-exist with or bypass old ones. Although the mechanisms involved in memory are still debated, they seem to require the involvement of cellular and molecular events, such as reorganisation of homo and heteroreceptor complexes at the synapse, synaptic plasticity, and epigenetic re-modulation of gene expression. Since SIGMAR1 mobilises synaptic receptor, boosts synaptic plasticity and modulates epigenetic processes, such effects might be involved in the reported healing of traumatic memories in PTSD patients. If this theory proves to be true, Ayahuasca could come to represent the only standing pharmacological treatment which targets traumatic memories in PTSD. Lastly, since SIGMAR1 activation triggers both epigenetic and immunomodulatory programmes, the mechanism here presented could help understanding and treating other conditions in which the cellular memory is dysregulated, such as cancer, diabetes, autoimmune and neurodegenerative pathologies and substance addiction.
Inserra, A. (2018). Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process. Frontiers in pharmacology9, 330. 10.3389/fphar.2018.00330
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Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy.

Abstract

A growing body of evidence shows that existential and spiritual well-being in cancer patients is associated with better medical outcomes, improved quality of life, and serves as a buffer against depression, hopelessness, and desire for hastened death. Historical and recent research suggests a role for psilocybin-assisted psychotherapy in treating cancer-related anxiety and depression. A double-blind controlled trial was performed, where 29 patients with cancer-related anxiety and depression were randomly assigned to treatment with single-dose psilocybin (0.3 mg/kg) or niacin in conjunction with psychotherapy. Previously published results of this trial demonstrated that, in conjunction with psychotherapy, moderate-dose psilocybin produced rapid, robust, and enduring anxiolytic, and anti-depressant effects. Here, we illustrate unique clinical courses described by four participants using quantitative measures of acute and persisting effects of psilocybin, anxiety, depression, quality of life, and spiritual well-being, as well as qualitative interviews, written narratives, and clinician notes. Although the content of each psilocybin-assisted experience was unique to each participant, several thematic similarities and differences across the various sessions stood out. These four participants’ personal narratives extended beyond the cancer diagnosis itself, frequently revolving around themes of self-compassion and love, acceptance of death, and memories of past trauma, though the specific details or narrative content differ substantially. The results presented here demonstrate the personalized nature of the subjective experiences elicited through treatment with psilocybin, particularly with respect to the spiritual and/or psychological needs of each patient.
Malone, T. C., Mennenga, S. E., Guss, J., Podrebarac, S. K., Owens, L. T., Bossis, A. P., … & Ross, S. (2018). Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy. Frontiers in pharmacology9, 256, 10.3389/fphar.2018.00256
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Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine

Abstract

Opioid use disorder (OUD) is currently an epidemic in the United States (US) and ibogaine is reported to have the ability to interrupt opioid addiction by simultaneously mitigating withdrawal and craving symptoms. This study examined opioid withdrawal and drug craving scores in 50 participants with OUD undergoing a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index (ASI) was used for baseline characterization of participants’ OUD. Clinical Opioid Withdrawal Scale (COWS), Subjective Opioid Withdrawal Scale (SOWS), and Brief Substance Craving Scale (BSCS) scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were significantly lowered in comparison to baseline: 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Ibogaine appears to facilitate opioid detoxification by reducing opioid withdrawal and craving in participants with OUD. These results warrant further research using rigorous controlled trials.
Malcolm, B. J., Polanco, M., & Barsuglia, J. P. (2018). Changes in Withdrawal and Craving Scores in Participants Undergoing Opioid Detoxification Utilizing Ibogaine. Journal of psychoactive drugs, 1-10. 10.1080/02791072.2018.1447175
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Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression

Abstract

BACKGROUND:
Natural speech analytics has seen some improvements over recent years, and this has opened a window for objective and quantitative diagnosis in psychiatry. Here, we used a machine learning algorithm applied to natural speech to ask whether language properties measured before psilocybin for treatment-resistant can predict for which patients it will be effective and for which it will not.
METHODS:
A baseline autobiographical memory interview was conducted and transcribed. Patients with treatment-resistant depression received 2 doses of psilocybin, 10 mg and 25 mg, 7 days apart. Psychological support was provided before, during and after all dosing sessions. Quantitative speech measures were applied to the interview data from 17 patients and 18 untreated age-matched healthy control subjects. A machine learning algorithm was used to classify between controls and patients and predict treatment response.
RESULTS:
Speech analytics and machine learning successfully differentiated depressed patients from healthy controls and identified treatment responders from non-responders with a significant level of 85% of accuracy (75% precision).
CONCLUSIONS:
Automatic natural language analysis was used to predict effective response to treatment with psilocybin, suggesting that these tools offer a highly cost-effective facility for screening individuals for treatment suitability and sensitivity.
LIMITATIONS:
The sample size was small and replication is required to strengthen inferences on these results.
Carrillo, F., Sigman, M., Slezak, D. F., Ashton, P., Fitzgerald, L., Stroud, J., … & Carhart-Harris, R. L. (2018). Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression. Journal of affective disorders230, 84-86. 10.1016/j.jad.2018.01.006
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Four weekly ayahuasca sessions lead to increases in “acceptance” capacities: a comparison study with a standard 8-week mindfulness training program

Abstract

Background: The therapeutic effects of the Amazonian plant tea ayahuasca may relate to its ability to enhance mindfulness capacities. Ayahuasca induces a modified state of awareness through the combined action of its active principles: the psychedelic N,N-dimethyltryptamine (DMT) and a series of centrally acting β-carbolines, mainly harmine and tetrahydroharmine. To better understand the therapeutic potential of ayahuasca, here we compared the impact on mindfulness capacities induced by two independent interventions: (a) participation in four ayahuasca sessions without any specific purpose related to improving mindfulness capacities; and (b) participation in a standard mindfulness training course: 8 weeks mindfulness-based stress reduction (MBSR), with the specific goal of improving these skills.

Methods: Participants of two independent groups completed two self-report instruments: The Five Facet Mindfulness Questionnaire (FFMQ) and the Experiences Questionnaire (EQ). The MINDSENS Composite Index was also calculated, including those EQ and FFMQ items that have proven to be the most sensitive to meditation practice. Group A (n = 10) was assessed before and after the last of four closely spaced consecutive ayahuasca sessions. Group B (n = 10) was assessed before and after completion of a standard 8-week MBSR course.

Results: MBSR training led to greater increases in overall mindfulness scores after the 8-week period. MBSR but not ayahuasca led to increases in the MINDSENS Composite Index. However, the ayahuasca sessions induced comparable increases in the Non-Judging subscale of the FFMQ, specifically measuring “acceptance.” Improving this capacity allows for a more detached and less judgmental stance toward potentially distressing thoughts and emotions.

Conclusion: The present findings suggest that a small number of ayahuasca sessions can be as effective at improving acceptance as more lengthy and costly interventions. Future studies should address the benefits of combining ayahuasca administration with mindfulness-based interventions. This will allow us to investigate if ayahuasca will improve the outcome of psychotherapeutic interventions.

Soler, J., Elices, M., Dominguez-Clave, E., Pascual, J. C., Feilding, A., Navarro-Gil, M., … & Riba, J. (2018). Four weekly ayahuasca sessions lead to increases in “acceptance” capacities: a comparison study with a standard 8-week mindfulness training program. Frontiers in Pharmacology9, 224. 10.3389/fphar.2018.00224
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