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Psychedelic Drugs in Biomedicine

September 22, 2017 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Substance Use Disorder / By / , , , ,

Abstract

Psychedelic drugs, such as lysergic acid diethylamide (LSD), mescaline, and psilocybin, exert profound effects on brain and behavior. After decades of difficulties in studying these compounds, psychedelics are again being tested as potential treatments for intractable biomedical disorders. Preclinical research of psychedelics complements human neuroimaging studies and pilot clinical trials, suggesting these compounds as promising treatments for addiction, depression, anxiety, and other conditions. However, many questions regarding the mechanisms of action, safety, and efficacy of psychedelics remain. Here, we summarize recent preclinical and clinical data in this field, discuss their pharmacological mechanisms of action, and outline critical areas for future studies of psychedelic drugs, with the goal of maximizing the potential benefits of translational psychedelic biomedicine to patients.
Kyzar, E. J., Nichols, C. D., Gainetdinov, R. R., Nichols, D. E., & Kalueff, A. V. (2017). Psychedelic Drugs in Biomedicine. Trends in Pharmacological Sciences. 10.1016/j.tips.2017.08.003
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Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review

September 22, 2017 / Anxiety Disorders / PTSD, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with life-threatening diseases, often associated with a low quality of life and a poor overall prognosis. 5-HT2A-receptor agonists (serotonergic hallucinogens, ‘psychedelics’) like lysergic acid diethylamide (LSD) and psilocybin were first investigated as therapeutic agents in the 1960s. Recently, after a long hiatus period of regulatory obstacles, interest in the clinical use of these substances has resumed. The current article provides a systematic review of studies investigating psychedelics in the treatment of symptoms of existential distress in life-threatening diseases across different periods of research, highlighting how underlying concepts have developed over time. A systematic search for clinical trials from 1960 to 2017 revealed 11 eligible clinical trials involving a total number of N=445 participants, of which 7 trials investigated the use of lysergic acid diethylamide (LSD) (N=323), 3 trials investigated the use of psilocybin (N=92), and one trial investigated the use of dipropyltryptamine (DPT) (N=30). The 4 more recent randomized controlled trials (RCTs) (N=104) showed a significantly higher methodological quality than studies carried out in the 1960s and 1970s. Evidence supports that patients with life threatening diseases associated with symptoms of depression and anxiety benefit from the anxiolytic and antidepressant properties of serotonergic hallucinogens. Some studies anecdotally reported improvements in patients´ quality of life and reduced fear of death. Moreover, low rates of side effects were reported in studies that adhered to safety guidelines. Further studies are needed to determine how these results can be transferred into clinical practice.
Reiche, S., Hermle, L., Gutwinski, S., Jungaberle, H., Gasser, P., & Majić, T. (2017). Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 10.1016/j.pnpbp.2017.09.012
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Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations

September 21, 2017 / LSD, Neuroscience, Papers, Publications / By / , , , , , ,

Abstract

OBJECTIVE:
It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system.
METHOD:
100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects.
RESULTS:
LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects.
CONCLUSION:
Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT2A -receptor in altered states of consciousness.
Mueller, F., Lenz, C., Dolder, P., Lang, U., Schmidt, A., Liechti, M., & Borgwardt, S. (2017). Increased thalamic resting‐state connectivity as a core driver of LSD‐induced hallucinations. Acta Psychiatrica Scandinavica. 10.1111/acps.12818
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Long-lasting subjective effects of LSD in normal subjects

September 16, 2017 / LSD, Papers, Psychology / By / ,

Abstract

Rationale

Lysergic acid diethylamide (LSD) and other serotonergic hallucinogens can induce profound alterations of consciousness and mystical-type experiences, with reportedly long-lasting effects on subjective well-being and personality.

Methods

We investigated the lasting effects of a single dose of LSD (200 μg) that was administered in a laboratory setting in 16 healthy participants. The following outcome measures were assessed before and 1 and 12 months after LSD administration: Persisting Effects Questionnaire (PEQ), Mysticism Scale (MS), Death Transcendence Scale (DTS), NEO-Five Factor Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI).

Results

On the PEQ, positive attitudes about life and/or self, positive mood changes, altruistic/positive social effects, positive behavioral changes, and well-being/life satisfaction significantly increased at 1 and 12 months and were subjectively attributed by the subjects to the LSD experience. Five-Dimensions of Altered States of Consciousness (5D-ASC) total scores, reflecting acutely induced alterations in consciousness, and Mystical Experience Questionnaire (MEQ30) total scores correlated with changes in well-being/life satisfaction 12 months after LSD administration. No changes in negative attitudes, negative mood, antisocial/negative social effects, or negative behavior were attributed to the LSD experience. After 12 months, 10 of 14 participants rated their LSD experience as among the top 10 most meaningful experiences in their lives. Five participants rated the LSD experience among the five most spiritually meaningful experiences in their lives. On the MS and DTS, ratings of mystical experiences significantly increased 1 and 12 months after LSD administration compared with the pre-LSD screening. No relevant changes in personality measures were found.

Conclusions

In healthy research subjects, the administration of a single dose of LSD (200 μg) in a safe setting was subjectively considered a personally meaningful experience that had long-lasting subjective positive effects.

Schmid, Y., & Liechti, M. E. (2017). Long-lasting subjective effects of LSD in normal subjects. Psychopharmacology, 1-11. 10.1007/s00213-017-4733-3
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Psychedelic pleasures: An affective understanding of the joys of tripping

September 13, 2017 / LSD, Mushrooms / Psilocybin, Papers, Philosophy & Religious Studies, Psychology, Publications / By /

Abstract

BACKGROUND:
This paper considers the pleasures of psychedelic drugs and proposes a Deleuzian understanding of drugged pleasures as affects. In spite of a large body of work on psychedelics, not least on their therapeutic potentials, the literature is almost completely devoid of discussions of the recreational practices and pleasures of entheogenic drugs. Yet, most people do not use psychedelics because of their curative powers, but because they are fun and enjoyable ways to alter the experience of reality.
METHODS:
In the analytical part of the paper, I examine 100 trip reports from an internet forum in order to explore the pleasures of tripping.
RESULTS:
The analyses map out how drugs such as LSD and mushrooms – in combination with contextual factors such as other people, music and nature – give rise to a set of affective modifications of the drug user’s capacities to feel, sense and act.
CONCLUSION:
In conclusion it is argued that taking seriously the large group of recreational users of hallucinogens is important not only because it broadens our understanding of how entheogenic drugs work in different bodies and settings, but also because it may enable a more productive and harm reductive transmission of knowledge between the scientific and recreational psychedelic communities.
Bøhling, F. (2017). Psychedelic pleasures: An affective understanding of the joys of tripping. International Journal of Drug Policy, 49, 133-143. 10.1016/j.drugpo.2017.07.017
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Psychedelic pleasures: An affective understanding of the joys of tripping

September 13, 2017 / Anthropology & Sociology, LSD, Mushrooms / Psilocybin, Papers, Philosophy & Religious Studies, Psychology, Publications / By /

Abstract

BACKGROUND:
This paper considers the pleasures of psychedelic drugs and proposes a Deleuzian understanding of drugged pleasures as affects. In spite of a large body of work on psychedelics, not least on their therapeutic potentials, the literature is almost completely devoid of discussions of the recreational practices and pleasures of entheogenic drugs. Yet, most people do not use psychedelics because of their curative powers, but because they are fun and enjoyable ways to alter the experience of reality.
METHODS:
In the analytical part of the paper, I examine 100 trip reports from an internet forum in order to explore the pleasures of tripping.
RESULTS:
The analyses map out how drugs such as LSD and mushrooms – in combination with contextual factors such as other people, music and nature – give rise to a set of affective modifications of the drug user’s capacities to feel, sense and act.
CONCLUSION:
In conclusion it is argued that taking seriously the large group of recreational users of hallucinogens is important not only because it broadens our understanding of how entheogenic drugs work in different bodies and settings, but also because it may enable a more productive and harm reductive transmission of knowledge between the scientific and recreational psychedelic communities.
Bøhling, F. (2017). Psychedelic pleasures: An affective understanding of the joys of tripping. International Journal of Drug Policy, 49, 133-143. 10.1016/j.drugpo.2017.07.017
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Psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches

September 5, 2017 / Anthropology & Sociology, Headache Pain and Neurological Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology / By / , ,

Abstract

Background

Treatment resistant cluster headache and migraine patients are exploring alternative treatments online. The aim of this study was to improve comprehension regarding the use of non-established or alternative pharmacological treatments used by sufferers of cluster headaches and migraines.

Methods

A qualitative thematic analysis of the users’ own accounts presented in online forum discussions were conducted. The forum boards https://shroomery.org/, http://bluelight.org, and https://clusterbusters.org/ met the inclusion criteria and were used for the study.

Results

The analysis resulted in six themes: a desperate need for effective treatments; the role of the forum—finding alternative treatments and community support; alternative treatment substances; dosage and regimens; effects and treatment results; and adverse effects. The results provide an insight into why, how, and by which substances and methods sufferers seek relief from cluster headache and migraines.

Conclusions

These patients are in a desperate and vulnerable situation, and illicit psychoactive substances are often considered a last resort. There appeared to be little or no interest in psychoactive effects per se as these were rather tolerated or avoided by using sub-psychoactive doses. Primarily, psilocybin, lysergic acid diethylamide, and related psychedelic tryptamines were reportedly effective for both prophylactic and acute treatment of cluster headache and migraines. Treatment results with cannabis were more unpredictable. No severe adverse events were reported, but it was observed how desperation sometimes spurred risky behavior when obtaining and testing various treatment alternatives. The forum discourse mainly revolved around maximizing treatment results and minimizing potential harms.

Andersson, M., Persson, M., & Kjellgren, A. (2017). Psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches. Harm Reduction Journal, 14(1), 60. 10.1186/s12954-017-0186-6

Interactions of Hallucinogens with the Glutamatergic System: Permissive Network Effects Mediated Through Cortical Layer V Pyramidal Neurons

August 23, 2017 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Publications / By /

Abstract

Recordings made from layer V (L5) pyramidal cells of the prefrontal cortex (PFC) and neocortex in rodent slice preparations have shown that serotonin (5-hydroxytryptamine, 5-HT) and serotonergic hallucinogens induce an increase in the frequency of spontaneous excitatory postsynaptic currents (EPSCs) in the apical dendritic field by activating 5-HT2A receptors. Serotonergic hallucinogens induce late EPSCs and increase recurrent network activity when subcortical or mid-cortical regions are stimulated at low frequencies (e.g., 0.1 Hz). A range of agonists or positive allosteric modulators (PAMs) for mostly Gi/o-coupled receptors, including metabotropic glutamate2 (mGlu2), adenosine A1, or μ-opioid receptors, suppress these effects of 5-HT2A receptor stimulation. Furthermore, a range of mostly Gq/11-coupled receptors (including orexin2 [OX2]; α1-adrenergic, and mGlu5 receptors) similarly induce glutamate (Glu) release onto L5 pyramidal cells. Evidence implicates a number of brain regions in mediating these effects of serotonergic hallucinogens and Gq/11-coupled receptors including the midline and intralaminar thalamic nuclei, claustrum, and neurons in deep PFC. These effects on 5-HT2Areceptors and related GPCRs appear to play a major role in the behavioral effects of serotonergic hallucinogens, such as head twitches in rodents and higher order behaviors such as rodent lever pressing on the differential-reinforcement-of-low rate 72-s (DRL 72-s) schedule. This implies that the effects of 5-HT2A receptor activation on the activity of L5 pyramidal cells may be responsible for mediating a range of behaviors linked to limbic circuitry with connectivity between the PFC, striatum, thalamus, claustrum, striatum, amygdala, and the hippocampal formation.

Marek, G. J. (2017). Interactions of Hallucinogens with the Glutamatergic System: Permissive Network Effects Mediated Through Cortical Layer V Pyramidal Neurons. 10.1007/7854_2017_480
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The 21st century psychedelic renaissance: heroic steps forward on the back of an elephant

August 23, 2017 / LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology / By /

Abstract

Given the plethora of new studies and published papers in the scientific press and the increasingly emerging presence of articles about positive psychedelic experiences appearing in the popular media, there is little doubt that we are in the midst of a Psychedelic Renaissance. The classical psychedelic drugs LSD and psilocybin and the entactogen MDMA are showing promise as tools to assist psychotherapy for a wide range of mental disorders, with multiple pilot studies demonstrating their safety and efficacy. In this article, the author describes how MDMA in particular has inherent characteristics that make it well suited for assisting trauma-focused psychotherapy in a population of patients who have experienced child abuse. But despite these advances, there remain many obstacles ahead of the widespread mainstream acceptance of psychedelic medicines. The author argues that the Misuse of Drugs Act 1971 is one such obstacle. Other impediments include a prevailing attitude of pseudoscience and rigidity from within the non-scientific psychedelic community itself. Resolution of these conflicts must be sought if medicine and society are to see psychedelics gaining a place in mainstream culture and science.
Sessa, B. (2017). The 21st century psychedelic renaissance: heroic steps forward on the back of an elephant. Psychopharmacology, 1-10. 10.1007/s00213-017-4713-7
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Psychedelics and connectedness

August 10, 2017 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Psychedelic drugs are creating ripples in psychiatry as evidence accumulates of their therapeutic potential. An important question remains unresolved however: how are psychedelics effective? We propose that a sense of connectedness is key, provide some preliminary evidence to support this, and suggest a roadmap for testing it further.
Carhart-Harris, R. L., Erritzoe, D., Haijen, E., Kaelen, M., & Watts, R. (2017). Psychedelics and connectedness. Psychopharmacology, 1-4. 10.1007/s00213-017-4701-y
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