Psychedelic Research Papers

This seminal review paper (2004) reviews the psychedelics literature up to this point. It specifically looks at how the psychedelics influence the brain (regions). The main conclusion is that psychedelics increase prefrontal cortical metabolism, and correlations have been developed between activity in specific brain areas and psychological elements of the psychedelic experience. The paper foreshadows the research on the practical uses of psychedelics for (mental) illnesses.

This seminal paper (2014) introduces the entropic brain hypothesis intending to build a bridge between neuroscience and psychoanalytic theories. The entropic brain hypothesis proposes two different forms of cognition, one being more 'critical' and unconstrained (whilst under psychedelics). It has become one of the major theories underlying our understanding of how psychedelics exert their therapeutic effects.

The REBUS and the anarchic brain hypothesis paper (2019) argues that psychedelics relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system.

This longitudinal survey study (n=654 > 535 > 379 > 315 > 212, with increasing dropout) gathered data from individuals at five different time points before and after they undertook a preregistered psychedelic experience, and assessed variables related to personality traits, intentions, and the set and setting to predict the acute effects of taking the psychedelic, as well as long-term outcomes of subjective well-being. Baseline trait variables, such as absorption, strongly influenced long-term well-being. However, acute variables such as the intention and intensity of having mystical experiences also positively influenced well-being up to four weeks after the psychedelic experience.

This 2015 observational survey study (n=135.000) investigated the association between lifetime psychedelic use (LSD, psilocybin, mescaline) and mental health problems, but found no indication of the increased likelihood for psychological distress, mental health treatment, suicidal behaviour, depression, or anxiety amongst psychedelic users (n=19.300). These results contest the justification for prohibiting psychedelics as a public health measure.

This manuscript (2020) presents new data on the affinity of psychedelic drugs at receptors, transporters, and ion channels. Psychedelics (phenylalkylamines specifically) are not as selective as generally believed (they bind to more receptors).

This review article (2009) offers hypothesis (currently being tested) on how psychedelics work and how research in this field and research on schizophrenia overlaps.

This review (1998) looks at the history of LSD as a possible treatment for alcoholism (AUD). It highlights the research that had been done and how psychedelics were subsequently relabelled as drugs of abuse.

This opinion article (2018) argues that context (set and setting) are of upmost important when working with psychedelics and proposes ways of optimising context/treatment models.

A prospective survey study (n=654) established a (weak to moderate) causal link between the use of psychedelics and nature-relatedness. This was mediated by the extent of ego-death and perceived relatedness to nature during the psychedelic experience. This paper argues that psychedelics may bring us closer to nature and that this might be a possible positive outcome that restores mental health, or at least is correlated with this.

This review (2018) investigates the models (e.g. medium/high dosage) of psychedelic therapy in both its historical context and possible future directions.

This theory-building article (2017) offers more evidence for the entropic brain hypothesis, a hypothesis that under psychedelics the brain reaches higher criticality and is more susceptible to set and setting (bottom-up information). The study serves as a (possible) framework for why psychedelics work so well for a variety of mental disorders (in combination with psychotherapy).

This commentary (2015) analyses emerging research on psychedelic drugs for therapeutic purposes that involve humans and considering both the potential benefits and the possible harmful effects of using psychedelics in combination with psychotherapy or counselling for mental disorders illness.

This systemic review (2020) presents the results of 34 modern studies into the long-term effects of classical psychedelics in humans beyond the 2-week follow-up. Mystical experiences, connectedness, emotional breakthrough, and increased neural entropy were correlated with long-term changes in personality, depression, spirituality, anxiety, well-being, substance misuse, meditative practices, and mindfulness. A lack of aversive side effects with properly-executed treatment is also highlighted.

This review (2015) looks at the influence of subjective (therapeutic) effects on the (treatment) outcomes of psychedelic experiences. This is put in context of the neuronal mechanism of psychedelics, but that relationship is still something that we know little about.

This review article (2018) looks at the pre- and post-prohibition clinical studies on psychedelics and offers strategic advice on the legal and regulatory hurdles.

In this commentary article (2008), Ben Sessa reflects on the studies into creativity and psychedelics and proposes that we get back to studying the link between the two.

This narrative review discusses how meditation and psychedelic drugs can alter states of consciousness. There is converging evidence that psychedelics and meditation can produce strong, short-term, and reversible disruptions of self-consciousness and underlying neural processes. However, experiences of “self-loss” are not uniform and can be decomposed in “narrative” aspects (e.g. loss of access to autobiographical information), as well as bodily and multisensory aspects (e.g. loss of body ownership). Finally, the authors consider long-term outcomes of experiences of self-loss on individual traits and prosocial behavior.

This retrospective survey study (n=893) investigated the relationship between psychedelics use, ego dissolution, personality traits, political perspectives, and nature relatedness, and found that psychedelic use was associated with liberal and anti-authoritarian political views, openness to new experiences, and nature-relatedness.

This review (2018) finds that music may play a larger (active) role in psychedelic therapy and could be responsible for (part of the positive) outcomes.

This review (2019), for a psychiatry audience, summarizes our current understanding of how psychedelics work, from 5HT2a agonism to more bottom-up processing.

This review (2018) investigates historic and current theories on how psychedelics work. The work is first grounded by describing the (subjective) effects of psychedelics. The paper concludes that a commonality between theories is that ‘normal’ brain processes are disturbed. Thus leading to more unconstrained thoughts under psychedelics.

This review (2018) examines the cellular pathways through which psychedelics act as anti-inflammatory agents by means of selectively blocking the expression of pro-inflammatory mediators and thereby modulating histone modifications and epigenetic signaling. It is thus hypothesized that psychedelics may be of therapeutic value to a wide range of inflammatory disorders in humans.

This popular commentary article (2020) describes the current resurrection of research into psychedelics (both neuroscience and therapeutic applications). It describes the evidence for the serotonin receptor (5-HT2a) agonism (psychedelics binding to that receptor) and the possible mechanisms through which long-lasting therapeutic effects can be found.

This perspective article (2018) looks at the evidence for meaning-enhancing as a mediator in psychedelic therapy, spirituality and outcomes on creativity.

This review (2020) finds that randomized clinical trials (RCTs) support the efficacy of various psychedelic-assisted therapies for mental health disorders.

This non-controlled, naturalistic, observational study (n=379) collected self-reported user data one day after a preregistered psychedelic experience, for the purpose of validating a questionnaire that can assess 'emotional breakthrough'. This new scale was sufficiently different from previous tools, such as the Mystical Experience Questionnaire (MEQ), while sensitive enough to detect dose-dependent differences in the experience and predict post-psychedelic changes in well-being.

This article (2017) lays out guidelines and core competencies for psychedelic therapists in training, which include empathetic abiding presence; trust enhancement; spiritual intelligence; knowledge of the physical and psychological effects of psychedelics; therapist self-awareness and ethical integrity; and proficiency in complementary techniques. It also highlights 12 domains of curricular training that include knowledge of history, neuropharmacology, best practices in set and setting, as well as therapeutic strategies and boundaries.

This survey study (n=343) suggests that naturalistic psychedelic use may be associated with reduced problematic alcohol consumption. This complements clinical studies that found similar results with smaller sample sizes.

This diary study investigates the "safe and beneficial" use of psychedelics in small quantities (microdosing; 10 micrograms LSD) to improve positive moods by evaluating positive and negative emotional states using the PANAS checklist and written reports. The study showed that microdosing of a psychedelic in clinical and non-clinical populations improved health habits, increased energy, and improved work effectiveness. Furthermore, smaller samples demonstrated alleviation of symptoms in migraine headaches, traumatic brain injury, pre-menstrual syndromes (PMS), shingles, and other such conditions that have not been previously associated with psychedelic use.