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Psychology

Psychedelics, Meditation, and Self-Consciousness

Abstract

In recent years, the scientific study of meditation and psychedelic drugs has seen remarkable developments. The increased focus on meditation in cognitive neuroscience has led to a cross-cultural classification of standard meditation styles validated by functional and structural neuroanatomical data. Meanwhile, the renaissance of psychedelic research has shed light on the neurophysiology of altered states of consciousness induced by classical psychedelics, such as psilocybin and LSD, whose effects are mainly mediated by agonism of serotonin receptors. Few attempts have been made at bridging these two domains of inquiry, despite intriguing evidence of overlap between the phenomenology and neurophysiology of meditation practice and psychedelic states. In particular, many contemplative traditions explicitly aim at dissolving the sense of self by eliciting altered states of consciousness through meditation, while classical psychedelics are known to produce significant disruptions of self-consciousness, a phenomenon known as drug-induced ego dissolution. In this article, we discuss available evidence regarding convergences and differences between phenomenological and neurophysiological data on meditation practice and psychedelic drug-induced states, with a particular emphasis on alterations of self-experience. While both meditation and psychedelics may disrupt self-consciousness and underlying neural processes, we emphasize that neither meditation nor psychedelic states can be conceived as simple, uniform categories. Moreover, we suggest that there are important phenomenological differences even between conscious states described as experiences of self-loss. As a result, we propose that self-consciousness may be best construed as a multidimensional construct, and that “self-loss,” far from being an unequivocal phenomenon, can take several forms. Indeed, various aspects of self-consciousness, including narrative aspects linked to autobiographical memory, self-related thoughts and mental time travel, and embodied aspects rooted in multisensory processes, may be differently affected by psychedelics and meditation practices. Finally, we consider long-term outcomes of experiences of self-loss induced by meditation and psychedelics on individual traits and prosocial behavior. We call for caution regarding the problematic conflation of temporary states of self-loss with “selflessness” as a behavioral or social trait, although there is preliminary evidence that correlations between short-term experiences of self-loss and long-term trait alterations may exist.

Millière, R., Carhart-Harris, R. L., Roseman, L., Trautwein, F. M., & Berkovich-Ohana, A. (2018). Psychedelics, meditation, and self-consciousness. Frontiers in psychology9.,  10.3389/fpsyg.2018.01475
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A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus

Abstract

The subgranular zone (SGZ) of dentate gyrus (DG) is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that newborn neurons in this region encode temporal information about partially overlapping contextual memories. The 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring compound capable of inducing a powerful psychedelic state. Recently, it has been suggested that DMT analogs may be used in the treatment of mood disorders. Due to the strong link between altered neurogenesis and mood disorders, we tested whether 5-MeO-DMT is capable of increasing DG cell proliferation. We show that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, using a transgenic animal expressing tamoxifen-dependent Cre recombinase under doublecortin promoter, we found that 5 Meo-DMT treated mice had a higher number of newborn DG Granule cells (GC). We also showed that these DG GC have more complex dendritic morphology after 5-MeO-DMT. Lastly, newborn GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. Our findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.

Lima, R. V., Moulin, T., Lintzmaier, L. P., & Leão, R. N. (2018). A single dose of 5-MeO-DMT stimulates cell proliferation, neuronal survivability, morphological and functional changes in adult mice ventral dentate gyrus. Frontiers in molecular neuroscience11, 312., 10.3389/fnmol.2018.00312

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d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders.

Abstract

Depression and anxiety are psychiatric diagnoses commonly associated with low quality of life and low percentage of responsiveness by patients treated with currently available drugs. Thus, research into alternative compounds to treat these disorders is essential to guarantee a patient’s remission. The last decade has witnessed a revamped interest for the application of psychedelic medicine for the treatment of mental disorders due to anecdotal reports and clinical studies which show that low doses of d-lysergic acid diethylamide (LSD) and psilocybin may have antidepressant effects. LSD and psilocybin have demonstrated mood-modulating properties likely due to their capacity to modulate serotonergic (5-HT), dopaminergic (DA) and glutamatergic systems. LSD, belonging to the category of “classic halluginogens,” interacts with the 5-HT system through 5HT1A, and 5HT2A receptors, with the DA system through D2 receptors, and indirectly also the glutamatergic neurotransmission thought the recruitment of N-methyl-d-aspartate (NMDA) receptors. Randomized clinical studies have confirmed its antidepressant and anxiolytic effects in humans. Thus, in this chapter, we will review the pharmacology of psychedelic drugs, report the most striking clinical evidence which substantiate the therapeutic potentials of these fascinating compounds in mood disorders, and look into the horizon of where psychedelic medicine is heading.
De, D. G., Enns, J. P., Nuñez, N. A., Posa, L., & Gobbi, G. (2018). d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders. Progress in brain research242, 69-96., 10.1016/bs.pbr.2018.07.008
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LSD Administered as a Single Dose Reduces Alcohol Consumption in C57BL/6J Mice.

Abstract

There is a substantive clinical literature on classical hallucinogens, most commonly lysergic acid diethylamide (LSD) for the treatment of alcohol use disorder. However, there has been no published research on the effect of LSD on alcohol consumption in animals. This study evaluated the effect of LSD in mice using a two-bottle choice alcohol drinking paradigm. Adult male C57BL/6J mice were exposed to ethanol to develop preference and divided into three groups of equal ethanol consumption, and then treated with single intraperitoneal injection of saline or 25 or 50 μg/kg LSD and offered water and 20% ethanol. The respective LSD-treated groups were compared to the control group utilizing a multilevel model for repeated measures. In mice treated with 50 μg/kg LSD ethanol consumption was reduced relative to controls (p= 0.0035), as was ethanol preference (p = 0.0024), with a group mean reduction of ethanol consumption of 17.9% sustained over an interval of 46 days following LSD administration. No significant effects on ethanol consumption or preference were observed in mice treated with 25 μg/kg LSD. Neither total fluid intake nor locomotor activity in the LSD-treated groups differed significantly from controls. These results suggest that classical hallucinogens in the animal model merit further study as a potential approach to the identification of targets for drug discovery and investigation of the neurobiology of addiction.
Alper, K., Dong, B., Shah, R., Sershen, H., & Vinod, K. Y. (2018). LSD administered as a single dose reduces alcohol consumption in C57BL/6J mice. Frontiers in pharmacology9, 994., 10.3389/fphar.2018.00994
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Therapeutic Potential Ascribed to Ayahuasca by Users in the Czech Republic

This article focuses on the therapeutic potential ascribed to ayahuasca by users in the Czech Republic. Following an online survey, the fieldwork among users of ayahuasca was carried out from November 2015 to December 2016. The research sample consisted of 46 persons (23 women and 23 men), who took part at least once in some type of ayahuasca ritual and/or were the facilitators of the ayahuasca sessions. We held semi-structured interviews with participants in order to discover the therapeutic potential of ayahuasca. Transcribed recordings were analyzed using the Grounded Theory Method. The results suggest that the intensity of effects produced by ayahuasca is not directly proportional to its therapeutic effect. According to the informants, ayahuasca is applicable in the treatment of drug addiction. They consider it to have a broad spectrum of therapeutic potential. This therapeutic potential could be based on memory recall.
Horák, M., Hasíková, L., & Verter, N. (2018). Therapeutic Potential Ascribed to Ayahuasca by Users in the Czech Republic. Journal of psychoactive drugs50(5), 430-436., 10.1080/02791072.2018.1511878
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It’s Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in Zebrafish

Abstract

Ayahuasca is a psychoactive brew traditionally used in shamanistic and vegetalistic rituals and has recently received lot of attention due to potential cognitive benefits. Ayahuasca effects are caused by the synergistic interaction of β-carbolines (harmine, harmaline and tetrahydroarmine) contained in Banisteriopsis caapi stalks combined with the N,N-dimethyltryptamine (DMT) from Psychotria viridis leaves, a potent agonist to serotonin (5-HT) receptors. The present study approaches the effects of chronic and acute exposure to two Ayahuasca concentrations (0.1 and 0.5 ml/L) on the cognitive ability to discriminate objects in a one-trial learning task in zebrafish. Based on the combination of concentrations and exposure regimens, we divided adult zebrafish in five treatment groups: acute 0.1 and 0.5 ml/L, chronic 0.1 and 0.5 ml/L, and control 0.0 (n = 20 for each group). Then we tested them in a memory task of object discrimination. Acute Ayahuasca exposed groups performed similarly to the control group, however chronically treated fish (13 days) presented both impaired discriminative performance and locomotor alterations. Overall, these results indicate that Ayahuasca is a potent psychoactive drug that, in chronic exposure, negatively affects mnemonic parameters in zebrafish. In single exposure it does not affects cognitive performance, but the higher concentration (0.5) affected locomotion. Moreover, we reinforce the importance of the zebrafish for behavioral pharmacological studies of drug screening, in special to psychedelic drug research.

Eduardo-da-Silva, P., Lobao-Soares, B., Amarilha, H., Pinheiro-da-Silva, J., Silva, P. F., & Luchiari, A. C. (2018). It’s tea time: Interference of Ayahuasca brew on discriminative learning in zebrafish. Frontiers in behavioral neuroscience12, 190., 10.3389/fnbeh.2018.00190

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It's Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in Zebrafish

Abstract

Ayahuasca is a psychoactive brew traditionally used in shamanistic and vegetalistic rituals and has recently received lot of attention due to potential cognitive benefits. Ayahuasca effects are caused by the synergistic interaction of β-carbolines (harmine, harmaline and tetrahydroarmine) contained in Banisteriopsis caapi stalks combined with the N,N-dimethyltryptamine (DMT) from Psychotria viridis leaves, a potent agonist to serotonin (5-HT) receptors. The present study approaches the effects of chronic and acute exposure to two Ayahuasca concentrations (0.1 and 0.5 ml/L) on the cognitive ability to discriminate objects in a one-trial learning task in zebrafish. Based on the combination of concentrations and exposure regimens, we divided adult zebrafish in five treatment groups: acute 0.1 and 0.5 ml/L, chronic 0.1 and 0.5 ml/L, and control 0.0 (n = 20 for each group). Then we tested them in a memory task of object discrimination. Acute Ayahuasca exposed groups performed similarly to the control group, however chronically treated fish (13 days) presented both impaired discriminative performance and locomotor alterations. Overall, these results indicate that Ayahuasca is a potent psychoactive drug that, in chronic exposure, negatively affects mnemonic parameters in zebrafish. In single exposure it does not affects cognitive performance, but the higher concentration (0.5) affected locomotion. Moreover, we reinforce the importance of the zebrafish for behavioral pharmacological studies of drug screening, in special to psychedelic drug research.

Eduardo-da-Silva, P., Lobao-Soares, B., Amarilha, H., Pinheiro-da-Silva, J., Silva, P. F., & Luchiari, A. C. (2018). It’s tea time: Interference of Ayahuasca brew on discriminative learning in zebrafish. Frontiers in behavioral neuroscience12, 190., 10.3389/fnbeh.2018.00190

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The influence of therapists’ first-hand experience with psychedelics on psychedelic-assisted psychotherapy research and therapist training

Clinical research on psychedelic-assisted psychotherapy is rapidly advancing in the USA, with two drugs, psilocybin and MDMA, progressing through a structure of FDA-approved trials on a trajectory toward Drug Enforcement Agency rescheduling for therapeutic use. Researcher’s and clinician’s personal use of psychedelics was cited as a potential confound in psychedelic research studies conducted in the 1950s and 1960s, a concern which contributed to the cessation of this research for some 20 years. Currently, there is no empirical research on personal use of psychedelics by current academic researchers and clinicians; its influence is undocumented, unknown, and undertheorized. This paper explores the history of personal use of psychedelics by clinicians and researchers, the potential impact of personal use on psychedelic-assisted psychotherapy and research, and the rationale for opening an academic discussion and program of research to investigate the role of personal use. We propose that there are factors unique to psychedelic-assisted therapy such that training for it cannot neatly fit into the framework of modern psychopharmacology training, nor be fully analogous to psychotherapy training in contemporary psychological and psychiatric settings. We argue that scientific exploration of the influence of therapists’ first-hand experience of psychedelics on psychedelic-assisted therapy outcomes is feasible, timely, and necessary for the future of clinical research.
Nielson, E. M., & Guss, J. (2018). The influence of therapists’ first-hand experience with psychedelics on psychedelic-assisted psychotherapy research and therapist training. Journal of Psychedelic Studies, 1-10. 10.1556/2054.2018.009
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Legitimate Medicine in the Age of Consumerism

Abstract

From the opioid epidemic and medical marijuana to abortion restrictions and physician-assisted suicide, disputes over the proper uses of medicine loom large in American life. Nowhere is this conflict more apparent than in federal drug control policy, which is premised on a clear distinction between legitimate “medical” uses and illicit “abuse.” Yet the Controlled Substances Act defines neither of these foundational concepts. While it is tempting to imagine medicine’s scope is limited to treating or preventing disease – rendering nontherapeutic drug use “abuse” – in fact medical practice has always included interventions that are not aimed at healing. This trend has only accelerated as medical practice has become increasingly consumer-oriented. From Adderall to Xanax, patients now routinely seek prescriptions not to treat diagnosable illnesses, but to relieve stress, improve productivity, and otherwise enhance quality of life.

As physicians increasingly prescribe psychoactive drugs to help healthy people obtain desirable mental states, distinguishing legitimate drug use from recreational abuse becomes ever more difficult. Having failed to acknowledge this challenge, the DEA, courts, and scholars have not offered a principled way to make this distinction, rendering drug control policy increasingly incoherent. As a result, doctors face criminal prosecution without clear standards governing prescribing, potentially valuable interventions are arbitrarily barred from the market, and millions seek the benefits of drugs without professional medical guidance to mitigate their risks.

Rather than being limited to therapeutic aims, medicine is better understood as the application of a loosely-defined set of knowledge and interventions that the law entrusts to specific professionals, with accompanying duties to use these tools to benefit patients. Medical practice includes treating and preventing illnesses, but can also include enhancing social and cognitive functioning and promoting the well-being of people whose challenges do not rise to the level of disorders. Discarding a narrow conception of medicine does not require abandoning the enforcement of drug laws or the policing of doctors. But acknowledging the expansiveness of medicine’s domain does argue for clarifying the scope of physicians’ criminal liability and pursuing new strategies for harnessing drugs’ benefits while mitigating their risks.

Lamkin, M. (2018). Legitimate Medicine in the Age of Consumerism., 10.2139/ssrn.3228692
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DMT Models the Near-Death Experience

Abstract

Near-death experiences (NDEs) are complex subjective experiences, which have been previously associated with the psychedelic experience and more specifically with the experience induced by the potent serotonergic, N,N-Dimethyltryptamine (DMT). Potential similarities between both subjective states have been noted previously, including the subjective feeling of transcending one’s body and entering an alternative realm, perceiving and communicating with sentient ‘entities’ and themes related to death and dying. In this within-subjects placebo-controled study we aimed to test the similarities between the DMT state and NDEs, by administering DMT and placebo to 13 healthy participants, who then completed a validated and widely used measure of NDEs. Results revealed significant increases in phenomenological features associated with the NDE, following DMT administration compared to placebo. Also, we found significant relationships between the NDE scores and DMT-induced ego-dissolution and mystical-type experiences, as well as a significant association between NDE scores and baseline trait ‘absorption’ and delusional ideation measured at baseline. Furthermore, we found a significant overlap in nearly all of the NDE phenomenological features when comparing DMT-induced NDEs with a matched group of ‘actual’ NDE experiencers. These results reveal a striking similarity between these states that warrants further investigation.
Timmermann, C., Roseman, L., Williams, L., Erritzoe, D., Martial, C., Cassol, H., … & Carhart-Harris, R. (2018). DMT models the near-death experience. Frontiers in psychology9, 1424., 10.3389/fpsyg.2018.01424
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