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Psychology

Heaven and Hell—A Phenomenological Study of Recreational Use of 4-HO-MET in Sweden

Abstract

The psychoactive substance 4-HO-MET (4-hydroxy-N-methyl-N-ethyltryptamine) with psychedelic qualities is one of many legal so-called Internet drugs. The aim of this qualitative study was to establish an understanding of what characterizes its recreational use. Very little is known about the effects of this substance. Twenty-five anonymous Swedish experience reports (from persons aged 18–30 years) from public Internet forums were analyzed using the Empirical Phenomenological Psychological Method. The analysis produced 37 categories that were compiled into nine general themes: (1) motivation, preparation and expectation; (2) initial effects; (3) change of perception; (4) unfiltered awareness and intensified flow of information; (5) lateral cognition; (6) border between subject and object is erased; (7) heaven; (8) hell; and (9) subsiding effects. An understanding of the chronological happenings, called The Process, appeared out of the general structure. Drastic changes in cognitive, emotional and bodily functions were described. The motivation for use seemed to be driven by a strong curiosity. The experiences shifted between “heaven” and “hell,” but participants appeared satisfied and ready to repeat the experience. The experiences described show great similarity with classic psychedelic substances as LSD or psilocybin. More research is needed about health hazards or possible therapeutic potentials.

Kjellgren, A., & Soussan, C. (2011). Heaven and Hell—A Phenomenological Study of Recreational Use of 4-HO-MET in Sweden. Journal of Psychoactive Drugs, 43(3), 211-219. http://dx.doi.org/10.1080/02791072.2011.605699
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Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain

Abstract

A growing body of evidence has pointed to the N-methyl-d-aspartate (NMDA) receptor antagonists as a potential therapeutic target for the treatment of major depression. The present study investigated the possibility of synergistic interactions between antidepressant imipramine with the uncompetitive NMDA receptor antagonist ketamine. Wistar rats were acutely treated with ketamine (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) and then subjected to forced swimming tests. The cAMP response element bindig (CREB) and brain-derived neurotrophic factor (BDNF) protein levels and protein kinase C (PKC) and protein kinase A (PKA) phosphorylation were assessed in the prefrontal cortex, hippocampus and amygdala by imunoblot. Imipramine at the dose of 10 mg/kg and ketamine at the dose of 5 mg/kg did not have effect on the immobility time; however, the effect of imipramine (10 and 20 mg/kg) was enhanced by both doses of ketamine. Ketamine and imipramine alone or in combination at all doses tested did not modify locomotor activity. Combined treatment with ketamine and imipramine produced stronger increases of CREB and BDNF protein levels in the prefrontal cortex, hippocampus and amygdala, and PKA phosphorylation in the hippocampus and amygdala and PKC phosphorylation in prefrontal cortex. The results described indicate that co-administration of antidepressant imipramine with ketamine may induce a more pronounced antidepressant activity than treatment with each antidepressant alone. This finding may be of particular importance in the case of drug-resistant patients and could suggest a method of obtaining significant antidepressant actions whilst limiting side effects.

Réus, G. Z., Stringari, R. B., Ribeiro, K. F.,  Ferraro, A. K.,  Vitto, M. F., Cesconetto, P., … Quevedo, J. (2011). Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain. Behavioural Brain Research, 221(1), 166-171. http://dx.doi.org/10.1016/j.bbr.2011.02.024
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Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects

Abstract

Rationale: This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior.

Objectives: This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions.

Methods: Participants were 18 adults (17 hallucinogennaïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up.

Results: Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects.

Conclusions: Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.

Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., & Jesse, R. (2011). Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology, 218(4), 649-665. http://dx.doi.org/10.1007/s00213-011-2358-5
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In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in MDMA and Hallucinogen Users

Abstract

Context:
Both hallucinogens and 3,4-methylenedioxy-methamphetamine (MDMA or “ecstasy”) have direct agonistic effects on postsynaptic serotonin 2A receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.

Objective:
To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin2Areceptor binding.

Design:
A positron emission tomography study of 24 young adult drug users and 21 nonusing control partici-pants performed with carbon 11 (11C)–labeled 3-amino-4-[2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzo-nitrile (DASB) and fluorine 18 (18F)–labeled altanserin, respectively. Scans were performed in the user group after a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n = 10) and MDMA-preferring users (n = 14).

Participants:
Twenty-four young adult users of MDMA and/or hallucinogenic drugs and 21 nonusing controls.

Main Outcome Measures:
In vivo cerebral SERT and serotonin 2A receptor binding.

Results:
Compared with nonusers, MDMA-preferring users showed significant decreases in SERT nondisplaceable binding potential (neocortex, −56%; pallidostriatum, −19%; and amygdala, −32%); no significant changes were seen in hallucinogen-preferring users. Both cortical and pallidostriatal SERT nondisplaceable binding potential was negatively correlated with the number of life-time MDMA exposures, and the time of abstinence from MDMA was positively correlated with subcortical, but not cortical, SERT binding. A small decrease in neocortical serotonin 2A receptor binding in the serotonin 2A receptor agonist users (both user groups) was also detected.

Conclusions
We found evidence that MDMA but not hallucinogen use is associated with changes in the cerebral presynaptic serotonergic transmitter system. Because hallucinogenic drugs primarily have serotonin 2A receptor agonistic actions, we conclude that the negative association between MDMA use and cerebral SERT binding is mediated through a direct presynaptic MDMA effect rather than by the serotonin 2A agonistic effects of MDMA. Our cross-sectional data suggest that subcortical, but not cortical, recovery of SERT binding might take place after several months of MDMA abstinence.

Erritzoe, D., Frokjaer, V. G., Holst, K. K., Christoffersen, M., Johansen, S. S., Svarer, C., … Knudsen, G. M. (2011). In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users. Archives of General Psychiatry, 68(6), 562-576. http://dx.doi.org/10.1001/archgenpsychiatry.2011.56
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Consumption of Ayahuasca by Children and Pregnant Women: Medical Controversies and Religious Perspectives

Abstract

In 2010, the Brazilian Government agency responsible for drug-related issues formulated official Resolutions that categorized the consumption of ayahuasca by pregnant women and children in the Santo Daime and Uniatildeo do Vegetal ayahuasca-based religions as an “exercise of parental rights.” Although ayahuasca groups do enjoy a relative degree of social legitimacy and formal legal recognition in Brazil, the participation of pregnant women and children nevertheless continues to provoke heated discussion. This article raises the main issues involved in the public debate over this subject. In the first part, a diverse group of biomedical and health specialists was consulted, and their opinions were briefly analyzed. In the second, a full interview with a follower of one branch of Santo Daime, mother of four children who took ayahuasca during all her pregnancies, and whose children all drink ayahuasca, is presented. Her interview reveals important cultural parameters of ayahuasca consumption. The article explores common themes and contradictions found between the biomedical, anthropological, and ayahuasca-users’ discourses. It raises central issues regarding the limits of freedom of religion and the state’s right to interfere in family matters. The following analysis also has implications regarding the role of science in influencing policy decisions on drug use.

Labate, B. C. (2011). Consumption of Ayahuasca by Children and Pregnant Women: Medical Controversies and Religious Perspectives. Journal of Psychoactive Drugs, 43(1), 27-35. http://dx.doi.org/10.1080/02791072.2011.566498
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Harm potential of magic mushroom use: A review

Abstract

In 2007, the Minister of Health of the Netherlands requested the CAM (Coordination point Assessment and Monitoring new drugs) to assess the overall risk of magic mushrooms. The present paper is an updated redraft of the review, written to support the assessment by CAM experts. It summarizes the literature on physical or psychological dependence, acute and chronic toxicity, risk for public health and criminal aspects related to the consumption of magic mushrooms.

In the Netherlands, the prevalence of magic mushroom use was declining since 2000 (last year prevalence of 6.3% in 2000 to 2.9% in 2005), and further declined after possession and use became illegal in December 2008.

The CAM concluded that the physical and psychological dependence potential of magic mushrooms was low, that acute toxicity was moderate, chronic toxicity low and public health and criminal aspects negligible. The combined use of mushrooms and alcohol and the quality of the setting in which magic mushrooms are used deserve, however, attention.

In conclusion, the use of magic mushrooms is relatively safe as only few and relatively mild adverse effects have been reported. The low prevalent but unpredictable provocation of panic attacks and flash-backs remain, however, a point of concern.

van Amsterdam, J., Opperhuizen, A., & van den Brink, W. (2011). Harm potential of magic mushroom use: a review. Regulatory toxicology and pharmacology, 59(3), 423-429. https://dx.doi.org/10.1016/j.yrtph.2011.01.006
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The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations

Abstract

Background: Recent findings suggest that the serotonergic system and particularly the 5-HT2A/1A receptors are implicated in visual processing and possibly the pathophysiology of visual disturbances including hallucinations in schizophrenia and Parkinson’s disease.

Methods: To investigate the role of 5-HT2A/1A receptors in visual processing the effect of the hallucinogenic 5-HT2A/1A agonist psilocybin (125 and 250 μg/kg vs. placebo) on the spatiotemporal dynamics of modal object completion was assessed in normal volunteers (n = 17) using visual evoked potential recordings in conjunction with topographic-mapping and source analysis. These effects were then considered in relation to the subjective intensity of psilocybin-induced visual hallucinations quantified by psychometric measurement.

Results: Psilocybin dose-dependently decreased the N170 and, in contrast, slightly enhanced the P1 component selectively over occipital electrode sites. The decrease of the N170 was most apparent during the processing of incomplete object figures. Moreover, during the time period of the N170, the overall reduction of the activation in the right extrastriate and posterior parietal areas correlated positively with the intensity of visual hallucinations.

Conclusions: These results suggest a central role of the 5-HT2A/1A-receptors in the modulation of visual processing. Specifically, a reduced N170 component was identified as potentially reflecting a key process of 5-HT2A/1A receptor–mediated visual hallucinations and aberrant modal object completion potential.

Kometer, M., Cahn, B. R., Andel, D., Carter, O. L., & Vollenweider, F. X. (2011). The 5-HT2A/1A Agonist Psilocybin Disrupts Modal Object Completion Associated with Visual Hallucinations. Biological Psychiatry, 69, 399–406. http://dx.doi.org/10.1016/j.biopsych.2010.10.002
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Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs

Abstract

Aims: In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias.

Design: We compared illicit ecstasy users and non-users while (1) excluding individuals with significant life-time exposure to other illicit drugs or alcohol; (2) requiring that all participants be members of the ‘rave’ subculture; and (3) testing all participants with breath, urine and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons.
Setting: Field study.
Participants: Fifty-two illicit ecstasy users and 59 non-users, aged 18–45 years.
Measurements: Battery of 15 neuropsychological tests tapping a range of cognitive functions.
Findings: We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic self-regulation, possibly reflecting increased impulsivity. However, this finding might have reflected a pre-morbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug. Conclusions In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings—including our own—and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users.
Halpern, J. H., Sherwood, A. R., Hudson, J. I., Gruber, S. Kozin, D., & Pope Jr., H. G. (2011). “Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs. Addiction, 106(4), 777-786. http://dx.doi.org/10.1111/j.1360-0443.2010.03252.x
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Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Abstract

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT(2) receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT(2A) receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT(2) and non-5-HT(2) receptors.

Halberstadt, A. L., & Geyer, M.A. (2011). Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology, 61(3), 364-381. http://dx.doi.org/10.1016/j.neuropharm.2011.01.017
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Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer

Abstract

Context: Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer.

Objective: To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety.

Design: A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin.

Setting: A clinical research unit within a large public sector academic medical center.

Participants: Twelve adults with advanced-stage cancer and anxiety.

Main Outcome Measures: In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment.

Results: Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance.

Conclusions: This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field.

Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer. Archives of General Psychiatry, 68(1), 71-78. http://dx.doi.org/10.1001/archgenpsychiatry.2010.116
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Online Event - Psychedelic Care in Recreational Settings - 3 October 2024

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