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European Psilocybin Seminar at Tyringham Hall

/ Publications /

Tyringham Hall In June 2017, a two-day seminar on psilocybin for European therapists and researchers took place at Tyringham Hall, in the UK. The event was organised by OPEN in collaboration with UK mental health company Compass Pathways.
During a wonderful weekend at Tyringham Hall, near Oxford in the UK, attendees were invited to learn from leading experts in psychedelic-assisted psychotherapy, to discuss necessary competencies and other requirements for clinical applications of psilocybin, and to better understand pathways towards regulatory approval and patient access.
Facilitated by leading experts in the field of psilocybin research and therapy from the US, Switzerland and the UK, the participants discussed competencies for (new) therapists aiming to conduct research into psilocybin for various clinical indications. Attendees could learn from both patients and therapists on the importance of preparing, and supporting people in psilocybin-facilitated treatment at NYU, Imperial College and in Switzerland.
This small meeting consisted of a great mixture of academic researchers, clinicians and therapists from all over Europe: Denmark, Sweden, Norway, Portugal, Switzerland, Germany, Czech Republic, the Netherlands, Israel and the United Kingdom. With serious discussions, plenty of time for everyone to connect and share experiences, in a breath-taking setting, this was an inspiring first meeting of like-minded researchers and clinicians.

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Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs)

/ Neuroscience, Papers / / , , ,

Abstract

BACKGROUND:
4-Thio-substituted phenethylamines (2C-T drugs) are potent psychedelics with poorly defined pharmacological properties. Because of their psychedelic effects, 2C-T drugs are sometimes sold as new psychoactive substances (NPSs). The aim of the present study was to characterize the monoamine receptor and transporter interaction profiles of a series of 2C-T drugs.
METHODS:
We determined the binding affinities of 2C-T drugs at monoamine receptors and transporters in human cells that were transfected with the respective receptors or transporters. We also investigated the functional activation of serotonergic 5-hydroxytryptamine 2A (5-HT2A) and 5-HT2B receptors, activation of human trace amine-associated receptor 1 (TAAR1), and inhibition of monoamine uptake transporters.
RESULTS:
2C-T drugs had high affinity for 5-HT2A and 5-HT2C receptors (1-54 nM and 40-350 nM, respectively). With activation potencies of 1-53 nM and 44-370 nM, the drugs were potent 5-HT2A receptor and 5-HT2B receptor, respectively, partial agonists. An exception to this were the benzylthiophenethylamines, which did not potently activate the 5-HT2B receptor (EC50 > 3000 nM). Furthermore, the compounds bound to serotonergic 5-HT1A and adrenergic receptors. The compounds had high affinity for the rat TAAR1 (5-68 nM) and interacted with the mouse but not human TAAR1. The 2C-T drugs did not potently interact with monoamine transporters (Ki > 4000 nM).
CONCLUSION:
The receptor binding profile of 2C-T drugs predicts psychedelic effects that are mediated by potent 5-HT2 receptor interactions.
Luethi, D., Trachsel, D., Hoener, M. C., & Liechti, M. E. (2017). Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs). Neuropharmacology. 10.1016/j.neuropharm.2017.07.012
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The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro

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

Abstract

Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches.
Morales-García, J. A., de la Fuente Revenga, M., Alonso-Gil, S., Rodríguez-Franco, M. I., Feilding, A., Perez-Castillo, A., & Riba, J. (2017). The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Scientific reports, 7, 5309. 10.1038%2Fs41598-017-05407-9
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Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats

/ Neuroscience, Papers, Psychiatry & Medicine, Salvia / Salvinorin A / / , , , , , ,

Abstract

Ethnopharmacological relevance

Salvia divinorum is a medicinal plant traditionally used in hallucinogenic ethnopharmacological practices and for its analgesic and antinflammatory properties. Its active compounds include diterpenes known as salvinorins which act as potent κ opioid receptor agonists.

Aim of the study

Given its effects in acute animal models of pain, as well as its antinflammatory attributes, we decided to investigate the analgesic effects of an SD extract in neuropathic (sciatic loose nerve ligature) and inflammatory (intra plantar carrageenan) pain models in rats. We also determined in this study the electrocorticographic changes to correlate similar hallucinogenic state and behavior as those produced in humans.

Material and methods

Mechanical and thermonociceptive responses, plantar test and von Frey assay, respectively, were measured in adult Wistar rats 30 min, 3 h and 24 h after the intraperitoneal administration of saline or an hydroponic SD extract. We also evaluated carbamazepine and celecoxib, as gold reference drugs, to compare its antinociceptive effects.

Results

Our results showed that administration of SD extract induced antialgesic effects in both neuropathic and inflammatory pain models. All those effects were blocked by nor-binaltorphimine (a Kappa opioid receptor antagonist). Moreover, it was observed an increase of the anterior power spectral density and a decrease in the posterior region as electrocorticographic changes.

Conclusion

The present investigation give evidence that SD is capable to reduce algesic response associated to neuropathic and inflammatory nociception. This study support therapeutic alternatives for a disabling health problem due to the long term pain with high impact on population and personal and social implications.

Simón-Arceo, K., González-Trujano, M. E., Coffeen, U., Fernández-Mas, R., Mercado, F., Almanza, A., … & Pellicer, F. (2017). Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats. Journal of Ethnopharmacology, 206, 115-124. 10.1016/j.jep.2017.05.016
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MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

/ MDMA, Neuroscience, Papers, Psychology, Publications / / , , , , , ,

Abstract

Previous research has shown that a single dose of MDMA induce a dissociative state, by elevating feelings of depersonalization and derealization. Typically, it is assumed that action on the 5-HT2A receptor is the mechanism underlying these psychedelic experiences. In addition, other studies have shown associations between dissociative states and biological parameters (heart rate, cortisol), which are elevated by MDMA. In order to investigate the role of the 5-HT2 receptor in the MDMA-induced dissociative state and the association with biological parameters, a placebo-controlled within-subject study was conducted including a single oral dose of MDMA (75 mg), combined with placebo or a single oral dose of the 5-HT2 receptor blocker ketanserin (40 mg). Twenty healthy recreational MDMA users filled out a dissociative states scale (CADSS) 90 min after treatments, which was preceded and followed by assessment of a number of biological parameters (cortisol levels, heart rate, MDMA blood concentrations). Findings showed that MDMA induced a dissociative state but this effect was not counteracted by pre-treatment with ketanserin. Heart rate was the only biological parameter that correlated with the MDMA-induced dissociative state, but an absence of correlation between these measures when participants were pretreated with ketanserin suggests an absence of directional effects of heart rate on dissociative state. It is suggested that the 5-HT2 receptor does not mediate the dissociative effects caused by a single dose of MDMA. Further research is needed to determine the exact neurobiology underlying this effect and whether these effects contribute to the therapeutic potential of MDMA.
Puxty, D. J., Ramaekers, J. G., de la Torre, R., Farré, M., Pizarro, N., Pujadas, M., & Kuypers, K. P. (2017). MDMA-induced dissociative state not mediated by the 5-HT2A receptor. Frontiers in pharmacology, 8, 455. 10.3389/fphar.2017.00455
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A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT)

/ Depressive Disorders, DMT, Papers, Psychology / / , , , ,

Abstract

N,N-dimethyltryptamine (DMT) is a psychoactive substance that has been gaining popularity in therapeutic and recreational use. This is a case of a physician who chronically took DMT augmented with phenelzine in an attempt to self-medicate refractory bipolar depression. His presentation of altered mental status, mania, and psychosis is examined in regards to his DMT use. This case discusses DMT, the possible uses of DMT, and the theorized mechanism of DMT in psychosis and treatment of depression, particularly involving its agonist activity at 5-HT1A, 5-HT2A, and 5-HT2C. It is also important to recognize the dangers of self-medication, particularly amongst physicians.
Brown, T., Shao, W., Ayub, S., Chong, D., Cornelius, C. A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT). Journal of Psychoactive Drugs. 10.1080/02791072.2017.1344898
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Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways

/ LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers / / ,

Abstract

The neuropsychological effects of naturally occurring psychoactive chemicals have been recognized for millennia. Hallucinogens, which include naturally occurring chemicals such as mescaline and psilocybin, as well as synthetic compounds, such as lysergic acid diethylamide (LSD), induce profound alterations of human consciousness, emotion, and cognition. The discovery of the hallucinogenic effects of LSD and the observations that LSD and the endogenous ligand serotonin share chemical and pharmacological profiles led to the suggestion that biogenic amines like serotonin were involved in the psychosis of mental disorders such as schizophrenia. Although they bind other G protein-coupled receptor (GPCR) subtypes, studies indicate that several effects of hallucinogens involve agonist activity at the serotonin 5-HT2Areceptor. In this chapter, we review recent advances in understanding hallucinogen drug action through characterization of structure, neuroanatomical location, and function of the 5-HT2A receptor.
López-Giménez, J. F., & González-Maeso, J. (2017). Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways. 10.1007/7854_2017_478
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The Effects of Hallucinogens on Gene Expression

/ LSD, Neuroscience, Papers / / ,

Abstract

The classic serotonergic hallucinogens, or psychedelics, have the ability to profoundly alter perception and behavior. These can include visual distortions, hallucinations, detachment from reality, and mystical experiences. Some psychedelics, like LSD, are able to produce these effects with remarkably low doses of drug. Others, like psilocybin, have recently been demonstrated to have significant clinical efficacy in the treatment of depression, anxiety, and addiction that persist for at least several months after only a single therapeutic session. How does this occur? Much work has recently been published from imaging studies showing that psychedelics alter brain network connectivity. They facilitate a disintegration of the default mode network, producing a hyperconnectivity between brain regions that allow centers that do not normally communicate with each other to do so. The immediate and acute effects on both behaviors and network connectivity are likely mediated by effector pathways downstream of serotonin 5-HT2A receptor activation. These acute molecular processes also influence gene expression changes, which likely influence synaptic plasticity and facilitate more long-term changes in brain neurochemistry ultimately underlying the therapeutic efficacy of a single administration to achieve long-lasting effects. In this review, we summarize what is currently known about the molecular genetic responses to psychedelics within the brain and discuss how gene expression changes may contribute to altered cellular physiology and behaviors.
Martin, D. A., & Nichols, C. D. (2017). The Effects of Hallucinogens on Gene Expression. 10.1007/7854_2017_479
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LSD treatment in Scandinavia: emphasizing indications and short-term treatment outcomes of 151 patients in Denmark

/ LSD, Papers, Psychology / /

Abstract

BACKGROUND:
New research has suggested the clinical use of lysergic acid diethylamide (LSD) and psilocybin in selected patient populations. However, concerns about the clinical use of LSD were advanced in a large Danish follow-up study that assessed 151 LSD-treated psychiatric patients approximately 25 years after their treatment in the 1960s.
AIMS:
The purpose of the present study was to give a retrospective account of the short-term outcome of LSD treatment in these 151 Danish psychiatric patients.
METHODS:
The LSD case material in the Danish State Archives consists of medical case records of 151 LSD-treated patients, who complained and received economic compensation with the LSD Damages Law. The author carefully read and reviewed the LSD case material.
RESULTS:
LSD was used to treat a wide spectrum of mental disorders. Independent of diagnoses, 52 patients improved, and 48 patients worsened acutely with the LSD treatment. In a subgroup of 82 neurotic patients, the LSD dose-index (number of treatments multiplied by the maximal LSD dose) indicated the risk of acute worsening. In another subgroup of 19 patients with obsessive-compulsive neurosis, five patients later underwent psychosurgery. A small subgroup of 12 patients was treated with psilocybin. The long-term outcome was poor in most of the patients.
CONCLUSIONS:
Despite the significant limitations to a retrospective design, this database warrants caution in mental health patients. The use of LSD and psilocybin in mental health patients may be associated with serious short- and long-term side effects. Until further trials with rigorous designs have cleared these drugs of their potential harms, their clinical utility in these groups of patients has not been fully clarified.
Larsen, J. K. (2017). LSD treatment in Scandinavia: emphasizing indications and short-term treatment outcomes of 151 patients in Denmark. Nordic Journal of Psychiatry, 1-7. 10.1080/08039488.2017.1336251
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Online survey – are you planning to use psychedelics?

/ Publications /

psychedelic surveyResearchers at Imperial College, London have started an online observational study into the acute and long-term psychological effects of psychedelics. OPEN is a sponsor of this study.

The researchers aim to recruit individuals who are planning to take a psychedelic drug on their own initiative. You can sign up at their website and will subsequently receive several surveys before and after their psychedelic experience.
So, if you are or know anyone who has planned to take a psychedelic in the near future, please encourage them to sign up! More information on this study can be found at the Psychedelic Survey website, on facebook or on twitter.

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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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