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Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects

June 15, 2011 / Mushrooms / Psilocybin, Mystical experiences, Papers, Personality, Psychology, Psychopharmacology, Publications, Safety, Spirituality / By / , , , , ,

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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Consumption of Ayahuasca by Children and Pregnant Women: Medical Controversies and Religious Perspectives

April 8, 2011 / Anthropology, Ayahuasca, Other subjects, Papers, Psychology, Publications, Religious studies, Safety / By /

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

April 1, 2011 / History, Mushrooms / Psilocybin, Other disciplines, Papers, Psychology, Publications, Safety, Sociology, Toxicology / By / , ,

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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Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs

February 15, 2011 / MDMA, Neuroscience, Other subjects, Papers, Psychology, Psychopharmacology, Publications, Safety, Toxicology / By / , , , , ,

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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Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer

January 3, 2011 / Anxiety disorders / PTSD, Depression, Mushrooms / Psilocybin, Mystical experiences, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety, Spirituality / By / , , , , , ,

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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Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum

December 3, 2010 / Other subjects, Papers, Psychology, Psychopharmacology, Publications, Safety, Salvia / Salvinorin A / By / , , , ,

Abstract

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 min for 60 min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 min (first time point) and definite subjective effects were no longer present at approximately 20 min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2A) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects.

Johnson, M. W., Maclean, K.A., Reissig, C. R., Prisinzano, T. E., & Griffiths, R. R. (2010). Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum. Drug and Alcohol Dependence, 115(1-2), 150-155. http://dx.doi.org/10.1016/j.drugalcdep.2010.11.005

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Methodology for and the determination of the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine

October 26, 2021 / Ayahuasca, Papers, Publications, Safety, Toxicology / By / , , , ,

Abstract

Ayahuasca, also known as caapi or yage among various South American groups, holds a highly esteemed and millennia-old position in these cultures’ medical and religious pharmacopeia. There is now an increasing interest in the potential for modern medical applications of ayahuasca, as well as concerns regarding its increasing potential for abuse. Toxicological and clinical research to address these issues will require information regarding its metabolism and clearance. Thus, a rapid, sensitive and specific method for characterization and quantitation of the major constituents and of the metabolites of ayahuasca in urine is needed. The present research provides a protocol for conducting such analyses. The characteristics of the method, conducted by sample dilution and using HPLC–electrospray ionization (ESI)–selected reaction monitoring (SRM)–tandem mass spectrometry, are presented. The application of the analytical protocol to urine samples collected from three individuals that were administered ayahuasca has also been demonstrated. The data show that the major metabolite of the hallucinogenic component of ayahuasca, N,N-dimethyltryptamine (DMT), is the corresponding N-oxide, the first time this metabolite has been described in in vivo studies in humans. Further, very little DMT was detected in urine, despite the inhibition of monoamine oxidase afforded by the presence of the harmala alkaloids in ayahuasca. The major harmala alkaloid excreted was tetrahydroharmine. Other excretion products and metabolites were also identified and quantified. The method described would be suitable for use in further toxicological and clinical research on ayahuasca.

McIlhenny, E. H., Riba, J., Barbanoj, M. J., Strassman, R., & Barker, S. A. (2011). Methodology for and the determination of the major constituents and metabolites of the Amazonian botanical medicine ayahuasca in human urine. Biomedical Chromatography, 25(9), 970-984. 10.1002/bmc.1551
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Assessment of addiction severity among ritual users of ayahuasca

October 1, 2010 / Addiction, Ayahuasca, Papers, Psychiatry, Psychology, Publications, Safety, Spirituality / By / , , , , , , ,

Abstract

Ayahuasca is a psychoactive beverage used for magico-religious purposes in the Amazon. Recently, Brazilian syncretic churches have helped spread the ritual use of ayahuasca abroad. This trend has raised concerns that regular use of this N,N-dimethyltryptamine-containing tea may lead to the medical and psychosocial problems typically associated with drugs of abuse. Here we assess potential drug abuse-related problems in regular ayahuasca users. Addiction severity was assessed using the Addiction Severity Index (ASI), and history of alcohol and illicit drug use was recorded. In Study 1, jungle-based ayahuasca users (n=56) were compared vs. rural controls (n=56). In Study 2, urban-based ayahuasca users (n=71) were compared vs. urban controls (n=59). Follow-up studies were conducted 1 year later. In both studies, ayahuasca users showed significantly lower scores than controls on the ASI Alcohol Use, and Psychiatric Status subscales. The jungle-based ayahuasca users showed a significantly higher frequency of previous illicit drug use but this had ceased at the time of examination, except for cannabis. At follow-up, abstinence from illicit drug use was maintained in both groups except for cannabis in Study 1. However, differences on ASI scores were still significant in the jungle-based group but not in the urban group. Despite continuing ayahuasca use, a time-dependent worsening was only observed in one subscale (Family/Social relationships) in Study 2. Overall, the ritual use of ayahuasca, as assessed with the ASI in currently active users, does not appear to be associated with the deleterious psychosocial effects typically caused by other drugs of abuse.

Fábregas, J. M., González, D., Fondevila, S., Cutchet, M., Fernández, X., Barbosa, P. C., Riba, J., … Bouso J. C. (2010). Assessment of addiction severity among ritual users of ayahuasca. Drug and Alcohol Dependence,  111(3), 257–261. http://dx.doi.org/10.1016/j.drugalcdep.2010.03.024
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Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies

September 20, 2010 / Mushrooms / Psilocybin, Papers, Psychology, Psychopharmacology, Psychosis, Publications, Safety / By / , , ,

Abstract

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and longterm subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1–4 oral doses of psilocybin (45–315mg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

Studerus, E., Kometer, M., Hasler, F., & Vollenweider, F. X. (2010). Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. Journal of Psychopharmacology, 25(11), 1434-1452. http://dx.doi.org/10.1177/0269881110382466
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The safety and efficacy of ±3,4-methylenedioxymethamphetamineassisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder

July 19, 2010 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety / By / , , , ,

Abstract

Case reports indicate that psychiatrists administered 3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as ‘Ecstasy’ resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n¼12) or inactive placebo (n¼8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician- Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.

Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., & Doblin, R. (2010). The safety and efficacy of ±3,4-methylenedioxymethamphetamineassisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology, 25(4), 439-452. http://dx.doi.org/10.1177/0269881110378371
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30 April - Q&A with Rick Strassman

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