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Mushrooms / Psilocybin

The hallucinogenic world of tryptamines: an updated review

April 16, 2015 / DMT, LSD, Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Psychology, Publications / By / , , , ,

Abstract

In the area of psychotropic drugs, tryptamines are known to be a broad class of classical or serotonergic hallucinogens. These drugs are capable of producing profound changes in sensory perception, mood and thought in humans and act primarily as agonists of the 5-HT2A receptor. Well-known tryptamines such as psilocybin contained in Aztec sacred mushrooms and N,N-dimethyltryptamine (DMT), present in South American psychoactive beverage ayahuasca, have been restrictedly used since ancient times in sociocultural and ritual contexts. However, with the discovery of hallucinogenic properties of lysergic acid diethylamide (LSD) in mid-1900s, tryptamines began to be used recreationally among young people. More recently, new synthetically produced tryptamine hallucinogens, such as alpha-methyltryptamine (AMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), emerged in the recreational drug market, which have been claimed as the next-generation designer drugs to replace LSD (‘legal’ alternatives to LSD). Tryptamine derivatives are widely accessible over the Internet through companies selling them as ‘research chemicals’, but can also be sold in ‘headshops’ and street dealers. Reports of intoxication and deaths related to the use of new tryptamines have been described over the last years, raising international concern over tryptamines. However, the lack of literature pertaining to pharmacological and toxicological properties of new tryptamine hallucinogens hampers the assessment of their actual potential harm to general public health. This review provides a comprehensive update on tryptamine hallucinogens, concerning their historical background, prevalence, patterns of use and legal status, chemistry, toxicokinetics, toxicodynamics and their physiological and toxicological effects on animals and humans.

Araújo, A. M., Carvalho, F., de Lourdes Bastos, M., de Pinho, P. G., & Carvalho, M. (2015). The hallucinogenic world of tryptamines: an updated review. Archives of toxicology, 1-23. https://dx.doi.org/10.1007/s00204-015-1513-x
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Protecting the human rights of people who use psychedelics

April 1, 2015 / LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Summary

In a recent Comment Ben Sessa1 explained how the War on the Drugs worldwide has impeded development of psychiatric treatment with psychedelics such as LSD (lysergic acid diethylamide) and psilocybin (found in magic mushrooms). Prohibition also had negative outcomes for the millions of individuals who find it worthwhile to use psychedelics in various cultural settings outside of those in the clinic.

Krebs, T. S. (2015). Protecting the human rights of people who use psychedelics. The Lancet, 2(4), 294.295. http://dx.doi.org/10.1016/S2215-0366(15)00084-X
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Current knowledge on the neurobiology of classical hallucinogens and their relevance for the treatment of mood and anxiety disorders

March 28, 2015 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Hallucinogenic substances have been used for millenia. Still, the scientific investigation into the effects and mechanisms of classical hallucinogens in humans has only commenced with the discovery of LSD by Albert Hofmann in 1943. In the 1960’s, there were more than a thousand clinical studies that reported promising therapeutic effects of LSD and psilocybin in psychiatric patients. Only recently, however, the neuropharmacological and neurobiological underpinnings of hallucinogenic drugs have undergone systematic investigations. Despite having different chemical structures, classical hallucinogens produce striking similar subjective and behavioral effects in both animals and humans. Activation of the serotonin 2A (5-HT2A) receptor is a core feature in hallucinogenic pharmacology. Recent neuroimaging studies have begun to elucidate the brain mechanisms underlying hallucinogen-induced changes of thought, perception, and mood. Among the many networks involved in hallucinogen-related states of consciousness, the prefrontal cortex and the limbic regions appear to be especially relevant to the putative antidepressant effects of classical hallucinogens. Furthermore, hallucinogens may foster neuroplastic adaptations within cortico-subcortical brain networks. This appears to be a promising mechanism with regard to future clinical studies into the effects of classical hallucinogens in depression and anxiety.

Kraehenmann, R. (2015). The Effect of Serotonin Receptor Manipulation On Brain Networks and Its Impact On Emotion Regulation. European Psychiatry, 30, 21. http://dx.doi.org/10.1016/S0924-9338(15)30016-X
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5HT2a Receptors – a New Target for Depression?

March 28, 2015 / Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Cortical 5HT2A receptors are largely expressed in layer 5 pyramidal neurons and appear to play a pivotal role in brain function in that they gate top-down descending inputs to local cortical microcircuits. There is evidence that they may play a role in depression in that the number of these receptors is increased in some people with depression and the augmenting action of atypical antipsychotics in depression is thought to be – at least in part – due to blockade of these receptors. We have explored this possibility by studying the effects of agonists at these receptors – the psychedelic drugs psilocybin and LSD. We found they had profound effects to reduce brain activity particularly in regions that higly express the 5HT2A receptor such as the default mode network [DMN]. As this region is overactive in depression this may explain the improvements in mood that users of psychedelic often report. Based on these findings a study of psilocybin in resistant depression has been funded by the UK MRC and will start in early 2015.

Nutt, D. (2015). 5HT2a Receptors–a New Target for Depression? European Psychiatry, 30, 35. http://dx.doi.org/10.1016/S0924-9338(15)30027-4
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The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making

March 28, 2015 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

Social cognition is a crucial factor influencing development, progress, and treatment of psychiatric disorders. However, social cognition skills are insufficiently targeted by current treatment approaches. In particular, patients suffering from depression show an increased negative reaction to social exclusion and deficits in empathy. The 5HT-1A/2A receptor agonist psilocybin has previously been shown to reduce the neural response to negative emotional stimuli. However, it is not known if this extends to negative social interaction and whether 5HT-1A/2A receptor stimulation induces changes in empathy. Given the clear need for improved treatment of socio-cognitive functioning in psychiatric disorders, it is important to better understand the neuronal and neuromodulatory substrates of social cognition.

In a double-blind, randomized, cross-over design we therefore investigated the neural response to ostracism after the acute administration of psilocybin (0.215mg/kg) and placebo in healthy volunteers using fMRI. Furthermore, we assessed cognitive and emotional empathy using the Multifaceted Empathy Test.

The neural response to social exclusion in the ACC – a brain region associated with ‘social pain”- was reduced after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin while no significant differences were found in cognitive empathy.

These results show that the 5HT-1A/2A receptor subtypes play an important role in the modulation of socio-cognitive functioning and therefore may be relevant for the treatment of social cognition deficits in psychiatric disorders. In particular, they may be important for the normalization of empathy deficits and increased negative reaction to social exclusion in depressed patients.

Preller, K. H., Pokorny, T., Krähenmann, R., Dziobek, I., Stämpfli, P., & Vollenweider, F. X. (2015). The Effect of 5-HT2A/1a Agonist Treatment On Social Cognition, Empathy, and Social Decision-making. European Psychiatry, 30, 22. http://dx.doi.org/10.1016/S0924-9338(15)30017-1
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Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice

March 27, 2015 / Mushrooms / Psilocybin, Papers, Publications / By / , , , , , ,

Abstract

The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

Zhuk, O., Jasicka-Misiak, I., Poliwoda, A., Kazakova, A., Godovan, V. V., Halama, M., & Wieczorek, P. P. (2015). Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice. Toxins, 7(4), 1018-1029. http://dx.doi.org/10.3390/toxins7041018
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Classic hallucinogens in the treatment of addictions

March 14, 2015 / Ayahuasca, DMT, Iboga / Ibogaine, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Addictive disorders are very common and have devastating individual and social consequences. Currently available treatment is moderately effective at best. After many years of neglect, there is renewed interest in potential clinical uses for classic hallucinogens in the treatment of addictions and other behavioral health conditions. In this paper we provide a comprehensive review of both historical and recent clinical research on the use of classic hallucinogens in the treatment of addiction, selectively review other relevant research concerning hallucinogens, and suggest directions for future research. Clinical trial data are very limited except for the use of LSD in the treatment of alcoholism, where a meta-analysis of controlled trials has demonstrated a consistent and clinically significant beneficial effect of high-dose LSD. Recent pilot studies of psilocybin-assisted treatment of nicotine and alcohol dependence had strikingly positive outcomes, but controlled trials will be necessary to evaluate the efficacy of these treatments. Although plausible biological mechanisms have been proposed, currently the strongest evidence is for the role of mystical or other meaningful experiences as mediators of therapeutic effects. Classic hallucinogens have an excellent record of safety in the context of clinical research. Given our limited understanding of the clinically relevant effects of classic hallucinogens, there is a wealth of opportunities for research that could contribute important new knowledge and potentially lead to valuable new treatments for addiction.

Bogenschutz, M. P., & Johnson, M. W. (2015). Classic hallucinogens in the treatment of addictions. Progress in Neuro-Psychopharmacology and Biological Psychiatry. http://dx.doi.org/10.1016/j.pnpbp.2015.03.002
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Psychedelics not linked to mental health problems or suicidal behavior: A population study

March 5, 2015 / Anxiety Disorders / PTSD, Depressive Disorders, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Psychotic Disorders, Publications, Substance Use Disorder / By / ,

Abstract

A recent large population study of 130,000 adults in the United States failed to find evidence for a link between psychedelic use (lysergic acid diethylamide, psilocybin or mescaline) and mental health problems. Using a new data set consisting of 135,095 randomly selected United States adults, including 19,299 psychedelic users, we examine the associations between psychedelic use and mental health. After adjusting for sociodemographics, other drug use and childhood depression, we found no significant associations between lifetime use of psychedelics and increased likelihood of past year serious psychological distress, mental health treatment, suicidal thoughts, suicidal plans and suicide attempt, depression and anxiety. We failed to find evidence that psychedelic use is an independent risk factor for mental health problems. Psychedelics are not known to harm the brain or other body organs or to cause addiction or compulsive use; serious adverse events involving psychedelics are extremely rare. Overall, it is difficult to see how prohibition of psychedelics can be justified as a public health measure.

Johansen, P. Ø., & Krebs, T. S. (2015). Psychedelics not linked to mental health problems or suicidal behavior: A population study. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114568039
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Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction

February 23, 2015 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for “complete” mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.

Garcia-Romeu, A., Griffiths, R. R., & Johnson, M. W. (2015). Psilocybin-occasioned Mystical Experiences in the Treatment of Tobacco Addiction. Current Drug Abuse Reviews, 7(3), 157-164. http://dx.doi.org/10.2174/1874473708666150107121331
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