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Ayahuasca

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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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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Experience of Music Used With Psychedelic Therapy: A Rapid Review and Implications.

March 30, 2020 / Ayahuasca, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Bonny Method of Guided Imagery and Music emerged following discontinuation of psychedelic therapy research in the early 1970s, but psychedelic therapy research has since revived. Music remains a vital component. This study examined participants’ experiences of music in psychedelic therapy research. A rapid review of qualitative and quantitative journal articles in four major databases was conducted in February to April, 2019, using the terms hallucinogens, psychedelic, “lysergic acid diethylamide,” psilocybin, ayahuasca, music, and/or “music therapy.” Of 406 articles retrieved, 10 were included (n = 180; 18-69 years old). Participants had varied backgrounds. Music was widely considered integral for meaningful emotional and imagery experiences and self-exploration during psychedelic therapy. Music transformed through its elicitation of anthropomorphic, transportive, synesthetic, and material sensations. Music could convey love, carry listeners to other realms, be something to “hold,” inspire, and elicit a deep sense of embodied transformation. Therapeutic influence was especially evident in music’s dichotomous elicitations: Music could simultaneously anchor and propel. Participant openness to music and provision of participant-centered music were associated with optimal immediate and longer-term outcomes. Many studies reported scarce details about the music used and incidental findings of music experienced. Further understanding of participants’ idiosyncratic and shared responses to music during drug therapy phases will inform optimal development of flexible music protocols which enhance psychedelic therapy. Music therapists could be involved in the psychedelic therapy research renaissance through assisting with research to optimize music-based protocols used. If psychedelics become approved medicines, music therapists may be involved in offering psychedelic therapy as part of therapeutic teams.

O’Callaghan, C., Hubik, D. J., Dwyer, J., Williams, M., & Ross, M. (2020). Experience of Music Used With Psychedelic Therapy: A Rapid Review and Implications. Journal of Music Therapy., https://doi.org/10.1093/jmt/thaa006
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Reviewing the Potential of Psychedelics for the Treatment of PTSD.

March 14, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Ketamine, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

There are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line treatment for PTSD. Yet, even after psychotherapy, PTSD often remains a chronic illness, with high rates of psychiatric and medical comorbidity. Meanwhile, the search and development of drugs with new mechanisms of action has stalled. Therefore, there is an urgent need to explore not just novel compounds, but novel approaches for the treatment of PTSD. A promising new approach involves the use of psychedelic drugs. Within the past few years, two psychedelics have received breakthrough designations for psychiatric indications from the US Food and Drug Administration, and several psychedelics are currently being investigated for the treatment of PTSD. This review discusses four types of compounds: 3,4-methylenedioxymethamphetamine (MDMA), ketamine, classical psychedelics (e.g. psilocybin and LSD) and cannabinoids. We describe the therapeutic rationale, the setting in which they are being administered, and their current state of evidence in the treatment of PTSD. Each compound provides unique qualities for the treatment of PTSD, from their use to rapidly target symptoms, to their use as adjuncts to facilitate psychotherapeutic treatments. Several questions are formulated that outline an agenda for future research.
Krediet, E., Bostoen, T., Breeksema, J., van Schagen, A., Passie, T., & Vermetten, E. (2020). Reviewing the Potential of Psychedelics for the Treatment of PTSD. International Journal of Neuropsychopharmacology., https://doi.org/10.1093/ijnp/pyaa018
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Natural Psychoplastogens As Antidepressant Agents

March 5, 2020 / Ayahuasca, Depressive Disorders, DMT, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

Increasing prevalence and burden of major depressive disorder presents an unavoidable problem for psychiatry. Existing antidepressants exert their effect only after several weeks of continuous treatment. In addition, their serious side effects and ineffectiveness in one-third of patients call for urgent action. Recent advances have given rise to the concept of psychoplastogens. These compounds are capable of fast structural and functional rearrangement of neural networks by targeting mechanisms previously implicated in the development of depression. Furthermore, evidence shows that they exert a potent acute and long-term positive effects, reaching beyond the treatment of psychiatric diseases. Several of them are naturally occurring compounds, such as psilocybin, N,N-dimethyltryptamine, and 7,8-dihydroxyflavone. Their pharmacology and effects in animal and human studies were discussed in this article.

Benko, J., & Vranková, S. (2020). Natural Psychoplastogens As Antidepressant Agents. Molecules, 25(5), 1172., https://doi.org/10.3390/molecules25051172
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Subacute Effects of the Psychedelic Ayahuasca on the Salience and Default Mode Networks

February 21, 2020 / Ayahuasca, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Background: Neuroimaging studies have just begun to explore the acute effects of psychedelics on large-scale brain networks’ functional organization. Even less is known about the neural correlates of subacute effects taking place days after the psychedelic experience. This study explores the subacute changes of primary sensory brain networks and networks supporting higher-order affective and self-referential functions 24 hours after a single session with the psychedelic ayahuasca.
Methods: We leveraged task-free functional magnetic resonance imaging data 1 day before and 1 day after a randomized placebo-controlled trial exploring the effects of ayahuasca in naïve healthy participants (21 placebo/22 ayahuasca). We derived intra- and inter-network functional connectivity of the salience, default mode, visual, and sensorimotor networks, and assessed post-session connectivity changes between the ayahuasca and placebo groups. Connectivity changes were associated with Hallucinogen Rating Scale scores assessed during the acute effects.
Results: Our findings revealed increased anterior cingulate cortex connectivity within the salience network, decreased posterior cingulate cortex connectivity within the default mode network, and increased connectivity between the salience and default mode networks 1 day after the session in the ayahuasca group compared to placebo. Connectivity of primary sensory networks did not differ between groups. Salience network connectivity increases correlated with altered somesthesia scores, decreased default mode network connectivity correlated with altered volition scores, and increased salience default mode network connectivity correlated with altered affect scores.
Conclusion: These findings provide preliminary evidence for subacute functional changes induced by the psychedelic ayahuasca on higher-order cognitive brain networks that support interoceptive, affective, and self-referential functions.

Pasquini, L., Palhano-Fontes, F., & de Araujo, D. B. (2019). Subacute effects of the psychedelic ayahuasca on the salience and default mode networks. medRxiv, 19007542., https://doi.org/10.1177/0269881120909409
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A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses

January 30, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Psychotic Disorders, Publications, Substance Use Disorder / By / ,

Abstract

Though there was initial interest in the use of psychedelic drugs for psychiatric treatment, bad outcomes and subsequent passage of the Substance Act of 1970, which placed psychedelic drugs in the Schedule I category, significantly limited potential progress. More recently, however, there has been renewal in interest and promise of psychedelic research. The purpose of this review is to highlight contemporary human studies on the use of select psychedelic drugs, such as psilocybin, LSD, MDMA and ayahuasca, in the treatment of various psychiatric illnesses, including but not limited to treatment-resistant depression, post-traumatic stress disorder, end-of-life anxiety, and substance use disorders. The safety and efficacy as reported from human and animal studies will also be discussed. Accumulated research to date has suggested the potential for psychedelics to emerge as breakthrough therapies for psychiatric conditions refractory to conventional treatments. However, given the unique history and high potential for misuse with popular distribution, special care and considerations must be undertaken to safeguard their use as viable medical treatments rather than drugs of abuse.

Chi, T., & Gold, J. A. (2020). A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses. Journal of the Neurological Sciences, 116715., 10.1016/j.jns.2020.116715
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A Dangerous Method? Psychedelic Therapy at Modum Bad, Norway, 1961-76

January 13, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

After many years of disregard, the use of psychedelic drugs in psychiatric treatment has re-emerged in recent years. The prospect that psychedelics may again be integrated into mainstream psychiatry has aroused interest in long-forgotten research and experience from the previous phase of psychedelic therapy, which lasted from the late 1940s to the 1970s. This article will discuss one large-scale psychedelic therapy programme at Modum Bad Nervesanatorium, a psychiatric clinic which treated 379 inpatients with psychedelic drugs during the years 1961-76. The psychiatrists there initially regarded the psychedelic treatment as efficacious and without serious negative reactions, but reports of long-term harm have since surfaced. This article discusses how insights from Modum Bad might benefit the new generation of psychedelic treatment efforts.
Johnstad, P. G. (2020). A dangerous method? Psychedelic therapy at Modum Bad, Norway, 1961–76. History of Psychiatry, 31(2), 217-226., https://doi.org/10.1177%2F0957154X19894537
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