Rationale: In recent decades, the use of ayahuasca (AYA) – a β-carboline- and dimethyltryptamine-rich hallucinogenic botanical preparation traditionally used by Northwestern Amazonian tribes for ritual and therapeutic purposes – has spread from South America to Europe and the USA, raising concerns about its possible toxicity and hopes of its therapeutic potential. Thus, it is important to...
In 2007, we proposed an explanation of delusion formation as aberrant prediction error-driven associative learning. Further, we argued that the NMDA receptor antagonist ketamine provided a good model for this process. Subsequently, we validated the model in patients with psychosis, relating aberrant prediction error signals to delusion severity. During the ensuing period, we have developed...
Since the wars in Iraq and Afghanistan, posttraumatic stress disorder (PTSD) has become a major area of research and development. The most widely accepted treatment for PTSD is prolonged exposure (PE) therapy, but for many patients it is intolerable or ineffective. ±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has recently re-emerged as a new treatment option, with...
Evidence suggests that hallucinogens may have therapeutic potential for addressing a variety of problem behaviors related to the externalizing spectrum of psychopathology, such as substance misuse and criminality. Intimate partner violence (IPV) is a prevalent form of criminal violence that is related to externalizing pathology. However, the association between hallucinogen use and IPV has not...
Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy...
The drug 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy", "molly") is a widely used illicit drug and experimental adjunct to psychotherapy. MDMA has unusual, poorly understood socioemotional effects, including feelings of interpersonal closeness and sociability. To better understand these effects, we conducted a small (n=12) within-subjects double-blind placebo controlled study of the...
In recent years the recreational use of inhaled nitrous oxide gas (N2O) is becoming increasingly popular, yet little is known about the characteristics of its users or the effects they experience. This paper presents original research from the 2014 Global Drug Survey (GDS) (n=74,864). GDS runs the largest survey of recreational drug use in the world. The findings confirm N2O as a very common...
This paper reports on the effects of LSD on mental time travel during spontaneous mentation. Twenty healthy volunteers participated in a placebo-controlled crossover study, incorporating intravenous administration of LSD (75 μg) and placebo (saline) prior to functional magnetic resonance imaging (fMRI). Six independent, blind judges analysed mentation reports acquired during structured...
The 30-item revised Mystical Experience Questionnaire (MEQ30) was previously developed within an online survey of mystical-type experiences occasioned by psilocybin-containing mushrooms. The rated experiences occurred on average eight years before completion of the questionnaire. The current paper validates the MEQ30 using data from experimental studies with controlled doses of psilocybin. Data...
Hendricks et al. (2015) found that having ever used any classic psychedelic substance—namely, dimethyltryptamine (DMT), ayahuasca, lysergic acid diethylamide (LSD), mescaline, peyote or San Pedro, or psilocybin—was associated with a significantly reduced likelihood of past month psychological distress (weighted OR = . 81 (. 72–. 91)), past year suicidal thinking (weighted OR = . 86 (. 78–....
Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for...
3,4-methylenedioxy- N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e....
Rationale: ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions. Method: Thirty-five healthy volunteers with prior MDMA experience completed this two-session,...
This study examined the overall psychological effects of inebriation facilitated by the naturally-occurring plant hallucinogen Salvia divinorum using a double-blind, randomized, placebo-controlled trial. Thirty healthy individuals self-administered Salvia divinorum via combustion and inhalation in a quiet, comfortable research setting. Experimental sessions, post-session interviews, and 8-week...
Background: 3,4-methylenedioxymethamphetamine (MDMA) produces “prosocial” effects that contribute to its recreational use. Few studies have examined the cognitive and behavioral mechanisms by which MDMA produces these effects. Here we examined the effect of MDMA on a specific prosocial effect, i.e. generosity, using a task in which participants make decisions about whether they or another...
Mental health problems are endemic across the globe, and suicide, a strong corollary of poor mental health, is a leading cause of death. Classic psychedelic use may occasion lasting improvements in mental health, but the effects of classic psychedelic use on suicidality are unknown. We evaluated the relationships of classic psychedelic use with psychological distress and suicidality among over...
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...
Anhedonia is a cardinal symptom of major depression and is often refractory to standard treatment, yet no approved medication for this specific symptom exists. In this exploratory re-analysis, we assessed whether administration of rapid-acting antidepressant ketamine was associated specifically with reduced anhedonia in medication-free treatment-refractory patients with major depressive...
Interest in the therapeutic potential of psychedelic substances has recently resumed. During an early phase of human psychedelic research, their therapeutic application in different pathologies had been suggested, and the first evidence for efficacy was provided. The range of recent clinical applications of psychedelics spans from cluster headaches and obsessive-compulsive disorder to addiction...
Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of...
Trait impulsivity has been linked to addiction in humans. It has been suggested that drug users with high trait impulsivity levels are more sensitive to subjective drug intoxication. This study assessed whether subjective response to drugs differs between drug users with normal or high levels of trait impulsivity. Regular drug users (N = 122) received doses of cocaine HCl, cannabis, and placebo...
Objective: A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases. Participants of this study were included in a prospective follow-up. Method: 12 months after finishing LSD psychotherapy, 10 participants were tested for anxiety (STAI) and participated in a semi-structured interview. A...
Ibogaine is an alkaloid purported to be an effective drug dependence treatment. However, its efficacy has been hard to evaluate, partly because it is illegal in some countries. In such places, treatments are conducted in underground settings where fatalities have occurred. In Brazil ibogaine is unregulated and a combined approach of psychotherapy and ibogaine is being practiced to treat...
Chronic cannabis use can cause cognitive, perceptual and personality alterations, which are believed to be associated with regional brain changes and possible changes in connectivity between functional regions. This study aims to identify the changes from resting state functional magnetic resonance imaging scans. A two-level multi-voxel pattern analysis was proposed to classify male cannabis...
Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a...