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Harmine stimulates proliferation of human neural progenitors

/ Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / / , , , , ,

Abstract

Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

Dakic, V., de Moraes Maciel, R., Drummond, H., Nascimento, J. M., Trindade, P., & Rehen, S. K. (2016). Harmine stimulates proliferation of human neural progenitors. PeerJ, 4, e2727. 10.7717/peerj.2727
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Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies

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

Abstract

Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies.

dos Santos, R. G., & Hallak, J. E. (2017). Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies. Journal of psychoactive drugs, 49(1), 1-10. 10.1080/02791072.2016.1260189
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How Religion, Race, and the Weedy Agency of Plants Shape Amazonian Home Gardens

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

Abstract

Across Brazilian Amazonia, it is common to find rural households that keep plants with magico-medicinal properties in their home gardens. Despite widespread occurrence of such plants, some Amazonians—especially in Evangelical communities—openly criticize their use as incongruent with Christian belief and practice. In this article, I offer ethnographic observations that indicate divergent attitudes toward magico-medicinal plants between Evangelical Christians and Amazonian folk Catholics, the latter of whom borrow heavily from Afro-Brazilian and indigenous religions. I contend that Evangelicals’ attempts to establish distance from such plants is due in part to histories of ethnic and racial marginalization that are indexed in their use. Still, many magico-medicinal plants are weedy species that actively colonize areas occupied by humans, thus openly defying Evangelical attempts to evade them. In this manner, magico-medicinal plants are not just subject to human agencies, but are arguably agents in their own right.

Kawa, N. C. (2016). How Religion, Race, and the Weedy Agency of Plants Shape Amazonian Home Gardens. Culture, Agriculture, Food and Environment, 38(2), 84-93. 10.1111/cuag.12073
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Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration

/ MDMA, Papers, Psychology, Publications, Substance Use Disorder / / ,

Abstract

Animal models of drug self-administration are currently the gold standard for making predictions regarding the relative likelihood that a recreational drug substance will lead to continued use and addiction. Such models have been found to have high predictive accuracy and discriminative validity for a number of drug classes including ethanol, nicotine, opioids, and psychostimulants such as cocaine and methamphetamine. Members of the entactogen class of psychostimulants (drugs that produce an “open mind state” including feelings of interpersonal closeness, intimacy and empathy) have been less frequently studied in self-administration models. The prototypical entactogen 3,4-methylenedioxymethamphetamine (MDMA; “Ecstasy”) supports self-administration but not with the same consistency nor with the same efficacy as structurally related drugs amphetamine or methamphetamine. Consistent with these observations, MDMA use is more episodic in the majority of those who use it frequently. Nevertheless, substantial numbers of MDMA users will meet the criteria for substance dependence at some point in their use history. This review examines the currently available evidence from rodent self-administration studies of MDMA and two of the new and emerging psychoactive substances (NPS) that produce entactogen type neuropharmacological responses – mephedrone (4-methylmethcathinone; 4MMC; “meow meow”) and methylone (3,4-methylenedioxymethcathinone). Overall, the current evidence predicts that these NPS entactogens have enhanced abuse liability compared with MDMA.

Aarde, S. M., & Taffe, M. A. (2016). Predicting the Abuse Liability of Entactogen-Class, New and Emerging Psychoactive Substances via Preclinical Models of Drug Self-administration. 10.1007/7854_2016_54
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The role of psychedelics in palliative care reconsidered: A case for psilocybin

/ Anxiety Disorders / PTSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , , ,

Kelmendi, B., Corlett, P., Ranganathan, M., D’Souza, C., & Krystal, J. H. (2016). The role of psychedelics in palliative care reconsidered: A case for psilocybin. Journal of psychopharmacology (Oxford, England), 30(12), 1212. 10.1177/0269881116675781
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Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology

/ Papers, Psychology, Publications / /

Abstract

Placebo response theory and set and setting theory are two fields which examine how non-biological factors shape the response to therapy. Both consider factors such as expectancy, preparation and beliefs to be crucial for understanding the extra-pharmacological processes which shape the response to drugs. Yet there are also fundamental differences between the two theories. Set and setting concerns itself with response to psychoactive drugs only; placebo theory relates to all therapeutic interventions. Placebo theory is aimed at medical professionals; set and setting theory is aimed at professionals and drug users alike. Placebo theory is primarily descriptive, describing how placebo acts; set and setting theory is primarily prescriptive, educating therapists and users on how to control and optimize the effects of drugs. This paper examines how placebo theory and set and setting theory can complement and benefit each other, broadening our understanding of how non-biological factors shape response to drugs and other treatment interventions.

Hartogsohn, I. (2016). Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology. Journal of Psychopharmacology, 0269881116677852.
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Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

/ Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / / , , , , , ,

Abstract

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.

Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., … & Su, Z. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of Psychopharmacology, 30(12), 1165-1180. 10.1177/0269881116675513
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Journal Club #22: Applying the EU Regulatory Framework to Determine the Benefit–Risk Profile of Psychedelics - March 3

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