OPEN Foundation

Author name: OPEN Foundation

Psilocybin for anxiety and depression in cancer care? Lessons from the past and prospects for the future

Nutt, D. (2016). Psilocybin for anxiety and depression in cancer care? Lessons from the past and prospects for the future. 10.1177/0269881116675754
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Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT

Abstract

3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.

Ma, K. H., Liu, T. T., Weng, S. J., Chen, C. F. F., Huang, Y. S., Chueh, S. H., … & Huang, W. S. (2016). Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT. Scientific Reports, 6. 10.1038/srep38695
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Ecstasy research: will increasing observational data aid our understanding of MDMA?

Abstract

Over the past three decades, millions of dollars have been spent on thousands of studies attempting to better understand the neurotoxic effects of MDMA. All of the clinical studies have recruited people who use ecstasy—a drug that does often but not always contain MDMA. Although most researchers agree that MDMA is the cause of neurocognitive deficits in ecstasy users, this consensus is based on a large body of literature with many limitations.

Amoroso, T. (2016). Ecstasy research: will increasing observational data aid our understanding of MDMA?. The Lancet Psychiatry, 3(12), 1101-1102. 10.1016/S2215-0366(16)30345-5
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The Therapeutic Potential of Ayahuasca

Abstract

Ayahuasca is a plant-based psychoactive decoction traditionally utilized by cultural groups throughout parts of Brazil, Peru, Colombia, Bolivia, Venezuela, and Ecuador during rites of passage, divination, warfare, magico-religious practices, and for healing in ethnomedical contexts. Over the last 150 years, ayahuasca has entered the global sphere and become a focus of scientific inquiry due to its reported use as an effective medicine to diagnose and treat illness. As a result, the use of ayahuasca within a healing context has become widespread and prompted researchers to investigate its putative therapeutic potential. In this chapter, the authors discuss current therapeutic applications of ayahuasca to treat addiction, depression, and anxiety. In this context, we highlight several studies to help facilitate a greater understanding of the therapeutic potential of ayahuasca.

Coe, M. A., & McKenna, D. J. (2017). The Therapeutic Potential of Ayahuasca. In Evidence-Based Herbal and Nutritional Treatments for Anxiety in Psychiatric Disorders (pp. 123-137). Springer International Publishing. 10.1007/978-3-319-42307-4_7

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Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats

Abstract

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, ‘foxy’) is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors. In this study, using microdialysis in freely moving rats, we examined the effect of 5-MeO-DIPT on dopamine (DA), serotonin (5-HT), and glutamate release in the rat striatum, nucleus accumbens, and frontal cortex. In search of a possible neurotoxic effect of 5-MeO-DIPT, we measured DA and 5-HT tissue content in the above rat brain regions and also determined the oxidative DNA damage with the comet assay. Moreover, we tested drug-elicited head-twitch response and a forepaw treading induced by 8-OH-DPAT. 5-MeO-DIPT at doses of 5, 10, and 20 mg/kg increased extracellular DA, 5-HT, and glutamate level but the differences in the potency were found between brain regions. 5-MeO-DIPT increased 5-HT and decreased 5-HIAA tissue content which seems to result from SERT inhibition. On the other hand, a decrease in DA, DOPAC, and HVA tissue contents suggests possible adaptive changes in DA turnover or damage of DA terminals by 5-MeO-DIPT. DNA single and double-strand breaks persisted up to 60 days after the treatment, indicating marked neurotoxicity of 5-MeO-DIPT. The induction of head-twitch response and potentiation of forepaw treading induced by 8-OH-DPAT indicate that hallucinogenic activity seems to be mediated through the stimulation of 5-HT2A and 5-HT1A receptors by 5-MeO-DIPT.
Noworyta-Sokołowska, K., Kamińska, K., Kreiner, G., Rogóż, Z., & Gołembiowska, K. (2016). Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats. Neurotoxicity research30(4), 606-619. 10.1007/s12640-016-9654-0
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Serotonergic Hallucinogen-Induced Visual Perceptual Alterations

Abstract

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT), are famous for their capacity to temporally and profoundly alter an individual’s visual experiences. These visual alterations show consistent attributes despite large inter- and intra-individual variances. Many reports document a common perception of colors as more saturated, with increased brightness and contrast in the environment (“Visual Intensifications”). Environmental objects might be altered in size (“Visual illusions”) or take on a modified and special meaning for the subject (“Altered self-reference”). Subjects may perceive light flashes or geometrical figures containing recurrent patterns (“Elementary imagery and hallucinations”) influenced by auditory stimuli (“Audiovisual synesthesia”), or they may envision images of people, animals, or landscapes (“Complex imagery and hallucinations”) without any physical stimuli supporting their percepts. This wide assortment of visual phenomena suggests that one single neuropsychopharmacological mechanism is unlikely to explain such vast phenomenological diversity. Starting with mechanisms that act at the cellular level, the key role of 5-HT2A receptor activation and the subsequent increased cortical excitation will be considered. Next, it will be shown that area specific anatomical and dynamical features link increased excitation to the specific visual contents of hallucinations. The decrease of alpha oscillations by hallucinogens will then be introduced as a systemic mechanism for amplifying internal-driven excitation that overwhelms stimulus-induced excitations. Finally, the hallucinogen-induced parallel decrease of the N170 visual evoked potential and increased medial P1 potential will be discussed as key mechanisms for inducing a dysbalance between global integration and early visual gain that may explain several hallucinogen-induced visual experiences, including visual hallucinations, illusions, and intensifications.

Kometer, M., & Vollenweider, F. X. (2016). Serotonergic Hallucinogen-Induced Visual Perceptual Alterations. 10.1007/7854_2016_461
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Ketamine’s Mechanisms of Rapid Antidepressant Activity: Evidence from Preclinical Studies

Abstract

Enthusiasm over the growing series of reports describing ketamine’s rapid onset of robust antidepressant activity in clinical trials has ignited a large number of back-translational efforts attempting to employ rodent models to better characterize the antidepressant properties of the drug and to improve our understanding of its underlying mechanisms of antidepressant action. On balance, these preclinical studies have yielded fairly consistent findings demonstrating that ketamine has a broad range of behavioral effects consistent with antidepressant activity in a variety of rodent models. Many of these studies further suggest that ketamine’s effects are unique from other classic antidepressant drugs in producing more durable effects in some models and more rapidly reversing the behavioral effects of chronic stressor exposure in other models. The preclinical studies are also beginning to elucidate the drug’s mechanisms of antidepressant activity, with the majority of recent studies suggesting that increased levels of regional alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor activation and brain-derived neurotrophic factor (BDNF) expression, as well as enhanced synaptic plasticity, are critical components of the response. However, there remain several points of disagreement and inconsistency in the preclinical literature that require additional investigation, including the effectiveness of other NMDA receptor-targeting drugs and the specific targets of ketamine’s proximal effects. This chapter provides an overview and critical review of this preclinical literature. It is anticipated that a more complete understanding of ketamine’s mechanisms of antidepressant action will allow for a safer and more efficient use of ketamine in the clinical setting and afford us new opportunities for novel drug development.

Hermes, G., & Sanacora, G. (2016). Ketamine’s Mechanisms of Rapid Antidepressant Activity: Evidence from Preclinical Studies. In Ketamine for Treatment-Resistant Depression (pp. 73-98). Springer International Publishing. 10.1007/978-3-319-42925-0_6

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Psycho-existential distress in cancer patients: A return to “entheogens”

Blinderman, C. D. (2016). Psycho-existential distress in cancer patients: A return to “entheogens”. Journal of Psychopharmacology, 30(12), 1205-1206. 10.1177/0269881116675761
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Back to the future: Research renewed on the clinical utility of psychedelic drugs

Lieberman, J. A., & Shalev, D. (2016). Back to the future: Research renewed on the clinical utility of psychedelic drugs. Journal of Psychopharmacology, 30(12), 1198-1200. 10.1177/0269881116675755
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Peer Perspectives: Economics and Real-World Data in Psychedelic Therapy Research - June 25