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Psilocybin for depression and anxiety associated with life-threatening illnesses

December 6, 2016 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

Life-threatening and terminal illnesses are accompanied by substantial stressors that encumber both patients and their families. Faced with a life-threatening diagnosis such as late-stage cancer, these factors can compound the existential crisis of impending mortality and produce or exacerbate major depressive and anxiety symptoms (Silverstone, 1990; Vergo et al., 2016). Addressing depression and anxiety in the unique context of life-threatening illnesses has been a significant problem for palliative psychiatric care. In this regard, two recent studies suggest that the one-time use of the naturally derived psychoactive compound psilocybin could have the potential to alleviate these symptoms for up to six months.

McCorvy, J. D., Olsen, R. H., & Roth, B. L. (2016). Psilocybin for depression and anxiety associated with life-threatening illnesses. Journal of psychopharmacology (Oxford, England), 30(12), 1209. 10.1177/0269881116675771
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Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder

December 6, 2016 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

OBJECTIVE: Insomnia and disrupted sleep are associated with increased risk of suicide. The N-methyl-D-aspartate antagonist ketamine has been associated with reduced suicidal thoughts, but the mechanism of action is unknown. This study sought to evaluate differences in nocturnal wakefulness in depressed individuals who did and did not have an antisuicidal response to ketamine.

METHODS: Thirty-four participants with baseline suicidal ideation diagnosed with either DSM-IV major depressive disorder (n = 23) or bipolar depression (n = 11) between 2006 and 2013 completed nighttime electroencephalography (EEG) the night before and the night after a single ketamine infusion (0.5 mg/kg over 40 minutes). Suicidal ideation was assessed at baseline and the morning after ketamine infusion via several measures, including the Hamilton Depression Rating Scale suicide item, the suicide item of the Montgomery-Asberg Depression Rating Scale, and the first 5 items of the Scale for Suicide Ideation. A generalized linear mixed model evaluated differences in nocturnal wakefulness, as verified by EEG, between those who had an antisuicidal response to ketamine and those who did not, controlling for baseline nocturnal wakefulness. Results were also compared to the sleep of healthy controls (n = 22).

RESULTS: After analyses adjusted for baseline sleep, participants with an antisuicidal response to ketamine showed significantly reduced nocturnal wakefulness the night after ketamine infusion compared to those without an antisuicidal response (F₁,₂₂ = 5.04, P = .04). Level of nocturnal wakefulness after antisuicidal response to ketamine did not differ significantly from nocturnal wakefulness in the control sample but did differ at a trend level (F₁,₄₀ = 3.15, P = .08).

CONCLUSIONS: Reductions in wakefulness following ketamine may point to a biological mechanism underlying the effect of ketamine on suicidal ideation.

Vande Voort, J. L., Ballard, E. D., Luckenbaugh, D. A., Bernert, R. A., Richards, E. M., Niciu, M. J., … & Zarate, C. A. (2016). Antisuicidal response following ketamine infusion is associated with decreased nighttime wakefulness in major depressive disorder and bipolar disorder. Journal of clinical psychiatry. 10.4088/JCP.15m10440
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Harmine stimulates proliferation of human neural progenitors

December 6, 2016 / Ayahuasca, Depressive Disorders, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

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

December 5, 2016 / Ayahuasca, Neuroscience, Papers, Psychology, Publications / By / ,

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

December 4, 2016 / Anthropology & Sociology, Ayahuasca, Biology & Ethnobotany, Papers, Publications / By /

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

December 2, 2016 / MDMA, Papers, Psychology, Publications, Substance Use Disorder / By / ,

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

December 1, 2016 / Anxiety Disorders / PTSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

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

December 1, 2016 / Papers, Psychology, Publications / By /

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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