Naturally occurring and psychedelic drug-occasioned experiences interpreted as personal encounters with God are well described but have not been systematically compared. In this study, five groups of individuals participated in an online survey with detailed questions characterizing the subjective phenomena, interpretation, and persisting changes attributed to their single most memorable God encounter experience (n = 809 Non-Drug, 1184 psilocybin, 1251 lysergic acid diethylamide (LSD), 435 ayahuasca, and 606 N,N-dimethyltryptamine (DMT)). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. The Non-Drug Group was most likely to choose “God” as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose “Ultimate Reality.” Although there were some other differences between non-drug and the combined psychedelic group, as well as between the four psychedelic groups, the similarities among these groups were most striking. Most participants reported vivid memories of the encounter experience, which frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. The encounter experience fulfilled a priori criteria for being a complete mystical experience in approximately half of the participants. More than two-thirds of those who identified as atheist before the experience no longer identified as atheist afterwards. These experiences were rated as among the most personally meaningful and spiritually significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences. Among the four groups of psychedelic users, the psilocybin and LSD groups were most similar and the ayahuasca group tended to have the highest rates of endorsing positive features and enduring consequences of the experience. Future exploration of predisposing factors and phenomenological and neural correlates of such experiences may provide new insights into religious and spiritual beliefs that have been integral to shaping human culture since time immemorial.
2012-09-27-nagel.txt: “A Philosopher Defends Religion [review of Plantinga, Where the Conflict Really Lies]”, (2012-09-27; ):
The gulf in outlook between atheists and adherents of the monotheistic religions is profound. We are fortunate to live under a constitutional system and a code of manners that by and large keep it from disturbing the social peace; usually the parties ignore each other. But sometimes the conflict surfaces and heats up into a public debate. The present is such a time.
…In his absorbing new book, Where the Conflict Really Lies, Alvin Plantinga, a distinguished analytic philosopher known for his contributions to metaphysics and theory of knowledge as well as to the philosophy of religion, turns this alleged opposition on its head. His overall claim is that “there is superficial conflict but deep concord between science and theistic religion, but superficial concord and deep conflict between science and naturalism.” By naturalism he means the view that the world describable by the natural sciences is all that exists, and that there is no such person as God, or anything like God. Plantinga’s religion is the real thing, not just an intellectual deism that gives God nothing to do in the world. He himself is an evangelical Protestant, but he conducts his argument with respect to a version of Christianity that is the “rough intersection of the great Christian creeds”—ranging from the Apostle’s Creed to the Anglican Thirty-Nine Articles—according to which God is a person who not only created and maintains the universe and its laws, but also intervenes specially in the world, with the miracles related in the Bible and in other ways. It is of great interest to be presented with a lucid and sophisticated account of how someone who holds these beliefs understands them to harmonize with and indeed to provide crucial support for the methods and results of the natural sciences…Faith, according to Plantinga, is another basic way of forming beliefs, distinct from but not in competition with reason, perception, memory, and the others. However, it is
a wholly different kettle of fish: according to the Christian tradition (including both Thomas Aquinas and John Calvin), faith is a special gift from God, not part of our ordinary epistemic equipment. Faith is a source of belief, a source that goes beyond the faculties included in reason.
God endows human beings with a sensus divinitatis that ordinarily leads them to believe in him. (In atheists the sensus divinitatis is either blocked or not functioning properly.)2 In addition, God acts in the world more selectively by “enabling Christians to see the truth of the central teachings of the Gospel.”
If all this is true, then by Plantinga’s standard of reliability and proper function, faith is a kind of cause that provides a warrant for theistic belief, even though it is a gift, and not a universal human faculty. (Plantinga recognizes that rational arguments have also been offered for the existence of God, but he thinks it is not necessary to rely on these, any more than it is necessary to rely on rational proofs of the existence of the external world to know just by looking that there is beer in the refrigerator.) It is illuminating to have the starkness of the opposition between Plantinga’s theism and the secular outlook so clearly explained. My instinctively atheistic perspective implies that if I ever found myself flooded with the conviction that what the Nicene Creed says is true, the most likely explanation would be that I was losing my mind, not that I was being granted the gift of faith. From Plantinga’s point of view, by contrast, I suffer from a kind of spiritual blindness from which I am unwilling to be cured. This is a huge epistemological gulf, and it cannot be overcome by the cooperative employment of the cognitive faculties that we share, as is the hope with scientific disagreements…The interest of this book, especially for secular readers, is its presentation from the inside of the point of view of a philosophically subtle and scientifically informed theist—an outlook with which many of them will not be familiar. Plantinga writes clearly and accessibly, and sometimes acidly—in response to aggressive critics of religion like Dawkins and Daniel Dennett. His comprehensive stand is a valuable contribution to this debate.
“What Happens When You Ask Questions to the DMT Entities?”, (2021-05-14):
Josikinz recently posted a wonderful video on Youtube titled “Psychedelic Entities—broken down and described”. I really appreciate the use of high-quality psychedelic replication art throughout the video in order to illustrate what they are talking about. I recommend watching the whole video; below an excerpt that discusses what happens when you try to ask these entities questions (starting at 10:53):
…Personal Commentary: …a substantial potion of the people who encounter them will go as far as to assert that these experiences are not simply fabrications of the mind, but rather beings from another world that exist independently of the human brain. This is a viewpoint that was originally popularized in mainstream culture by the likes of Terence McKenna, who famously theorized that the machine elves he encountered under the influence of DMT were either extraterrestrial in nature, interdimensional beings from a higher plane of existence, time-traveling humans from the future, or an ecology of souls that apparently includes both our ancestors and those who are yet to be born. As far as I can tell, the most common reasonings behind this viewpoint are that the experience of encountering these entities is often interpreted as feeling more realistic and well-defined than that of any sober experience the person has ever had. Alongside this, there is often a sense that the encounter itself is so incomprehensibly complex and other-worldly that there is simply no possible way that the human brain could generate such an experience on its own.
In regards to this particular notion, it is then sometimes asserted that consciousness must be an antenna of sorts that receives either all or some of its subjective experiences from that of an unknown interdimensional source. Furthermore, the source of this received input is sometimes said to be adjustable depending on the person’s brain state. With substances such as psychedelics simply “tuning” our consciousness into the analogous equivalent of a different radio station or TV channel. This is an idea that was once again further popularized by Terence McKenna, who is famously quoted as saying: “I don’t believe that consciousness is generated in the brain anymore than TV programs are made inside my TV. The box is too small.”
…In my personal opinion, if autonomous entities were truly something that exists beyond the human mind, I think there would likely be a single verifiable case of them conveying information to a person that they did not already know or could not have come to the conclusion of within that moment. This would also likely be testable to some degree, which has led myself and my close friends to casually experiment with asking DMT entities a variety of questions over the years [emphasis mine]. These questions have included math problems, metaphysical questions, philosophical questions, and queries pertaining to the general nature of beings inhabiting their particular world. However, each attempt at doing so has resulted in the entities simply ignoring the question, arrogantly scoffing at the absurdity of us asking them such a trivial thing, or replying with vague ambiguous wording that the person’s own mind could have easily come up with. This has even been the case when the entities are presenting themselves as vastly more complex, knowledgeable, and powerful than the humans that they are interacting with.
2017-carharttharris.pdf: “Serotonin and brain function: a tale of two receptors”, (2017-08-31; ):
Previous attempts to identify a unified theory of brain serotonin function have largely failed to achieve consensus. In this present synthesis, we integrate previous perspectives with new and older data to create a novel bipartite model centred on the view that serotonin neurotransmission enhances two distinct adaptive responses to adversity, mediated in large part by its two most prevalent and researched brain receptors: the 5-HT1A and 5-HT2A receptors. We propose that passive coping (ie. tolerating a source of stress) is mediated by postsynaptic 5-HT1AR signalling and characterised by stress moderation. Conversely, we argue that active coping (ie. actively addressing a source of stress) is mediated by 5-HT2AR signalling and characterised by enhanced plasticity (defined as capacity for change). We propose that 5-HT1AR-mediated stress moderation may be the brain’s default response to adversity but that an improved ability to change one’s situation and/or relationship to it via 5-HT2AR-mediated plasticity may also be important—and increasingly so as the level of adversity reaches a critical point. We propose that the 5-HT1AR pathway is enhanced by conventional 5-HT reuptake blocking antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), whereas the 5-HT2AR pathway is enhanced by 5-HT2AR-agonist psychedelics. This bipartite model purports to explain how different drugs (SSRIs and psychedelics) that modulate the serotonergic system in different ways, can achieve complementary adaptive and potentially therapeutic outcomes.
1999-aghajanian.pdf: “Serotonin and Hallucinogens”, (1999-08-01; ):
This brief review traces the serotonin (5-HT) hypothesis of the action of hallucinogenic drugs from the early 1950s to the present day. There is now converging evidence from biochemical, electrophysiological, and behavioral studies that the two major classes of psychedelic hallucinogens, the indoleamines (eg., LSD) and the phenethylamines (eg., mescaline), have a common site of action as partial agonists at 5-HT2A and other 5-HT2 receptors in the central nervous system. The noradrenergic locus coeruleus and the cerebral cortex are among the regions where hallucinogens have prominent effects through their actions upon a 5-HT2A receptors. Recently, we have observed a novel effect of hallucinogens—a 5-HT2A receptor-mediated enhancement of nonsynchronous, late components of glutamatergic excitatory postsynaptic potentials at apical dendrites of layer V cortical pyramidal cells. We propose that an effect of hallucinogens upon glutamatergic transmission in the may be responsible for the higher-level cognitive, perceptual, and affective distortions produced by these drugs.
The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe.
2004-knill.pdf: “The Bayesian brain: the role of uncertainty in neural coding and computation”, (2004-12; ):
To use sensory information efficiently to make judgments and guide action in the world, the brain must represent and use information about uncertainty in its computations for perception and action. Bayesian methods have proven successful in building computational theories for perception and sensorimotor control, and psychophysics is providing a growing body of evidence that human perceptual computations are ‘Bayes’ optimal’. This leads to the ‘Bayesian coding hypothesis’: that the brain represents sensory information probabilistically, in the form of probability distributions. Several computational schemes have recently been proposed for how this might be achieved in populations of neurons. Neurophysiological data on the hypothesis, however, is almost non-existent. A major challenge for neuroscientists is to test these ideas experimentally, and so determine whether and how neurons code information about sensory uncertainty.
Viewing the brain as an organ of approximate Bayesian inference can help us understand how it represents the self. We suggest that inferred representations of the self have a normative function: to predict and optimise the likely outcomes of social interactions. Technically, we cast this predict-and-optimise as maximising the chance of favourable outcomes through active inference. Here the utility of outcomes can be conceptualised as prior beliefs about final states. Actions based on interpersonal representations can therefore be understood as minimising surprise—under the prior belief that one will end up in states with high utility. Interpersonal representations thus serve to render interactions more predictable, while the affective valence of interpersonal inference renders self-perception evaluative. Distortions of self-representation contribute to major psychiatric disorders such as depression, personality disorder and paranoia. The approach we review may therefore operationalise the study of interpersonal representations in pathological states.
With due allowance for style and age, Hadamard ably describes and defends the basic model of ‘work, incubation, illumination, verification’, with reference to his own discoveries, his many famous acquaintances, Poincaré’s lecture, and a very interesting survey of mathematicians. In fact, it’s a little depressing that we don’t seem to have gone much beyond that in the half-century since this was published back in 1945 or so. While at least we no longer need his defense of the unconscious as a meaningful part of cognition, much of the rest is depressingly familiar—for example, his acute observations on mental imagery & people who solely think in words, and mention of Francis Galton’s survey (little-known outside of psychology), could be usefully read by many who commit the typical mind fallacy.
If Hadamard comes to no hard and fast conclusions, but merely raises many interesting points and criticizes a number of theories, we can hardly hold that against him, as we can do little better and so it becomes our failing to followup, not his.]
1955-abramson.pdf: “Lysergic Acid Diethylamide (LSD-25): Xv. the Effects Produced By Substitution of a Tap Water Placebo”, (1955; ):
The purpose of this paper is to study the responses given to a questionnaire by subjects who received a tap water ‘placebo’ instead of lysergic acid diethylamide (LSD-25), and to relate the number of responses to other variables. These variables are: body weight, number of responses on a health questionnaire, arithmetic test scores, scores on the Wechsler-Bellevue Intelligence Scale, and Rorschach test responses.
…Figure 4 shows for each question the percentage and number of subjects out of 28 who gave a positive response at least once during the 0.5, 2.5, and 4.5-hour intervals. The questions appear in the figure in the order of decreasing percentages of response to them. The time of the response and the magnitude are disregarded in this tabulation. The question receiving the greatest percentage response was (Subject 24), “Are your palms moist?” As many as 60.7% reported this symptom. Half of the subjects reported headache (Subject 13), fatigue (Subject 44), and drowsiness (Subject 45). About 36% reported anxiety (Subject 47). Illness (Subject 1), and dizziness (Subject 15) were reported by 28.6 per cent of the group and 25% indicated a dream-like feeling (Subject 46), increased appetite (Subject 6), unsteadiness (Subject 16), a hot feeling (Subject 22), heaviness of hands and feet (Subject 30), and weakness (Subject 43). There were 19 questions which received positive responses from between 10 and 22 per cent of the subjects. Less than 10% of the group (or no more than two subjects) responded positively to the remaining questions, but each question received a positive response from at least one subject.
…The findings point out that a substance such as tap water, which is generally considered chemically and pharmacologically inactive, is capable of eliciting certain responses from certain subjects who believe they have received lysergic acid diethylamide. These observations emphasize once more the need for placebo controls in studies investigating the effects of drugs; without them changes which are produced merely by the situation and not by the drug are frequently falsely attributed to the action of the drug…Most subjects who respond to a placebo tend to do so most markedly during the first 0.5 hour after receiving the substance. At this time their anticipation of, and anxiety about, the effects of LSD-25 are probably greatest. Gradually the effects wear off, as the anticipation wears off. Individual differences exist in the time of peak effect, but this is the most common finding. The questions which elicited the greatest percentage response from the group were those related to anxiety (moist palms and feeling anxious) or to phenomena which commonly occur without the presence of any foreign agent (drowsiness, fatigue, and headache). The remaining questions received random responses. The fact that there is a wide range in the number of positive responses made to the questionnaire is of major interest.
2020-olson.pdf: “Tripping on nothing: placebo psychedelics and contextual factors”, (2020-03-07; ):
Rationale: Is it possible to have a psychedelic experience from a placebo alone? Most psychedelic studies find few effects in the placebo control group, yet these effects may have been obscured by the study design, setting, or analysis decisions.
Objective: We examined individual variation in placebo effects in a naturalistic environment resembling a typical psychedelic party.
Methods: 33 students completed a single-arm study ostensibly examining how a psychedelic drug affects creativity. The 4-h study took place in a group setting with music, paintings, coloured lights, and visual projections. Participants consumed a placebo that we described as a drug resembling psilocybin, which is found in psychedelic mushrooms. To boost expectations, confederates subtly acted out the stated effects of the drug and participants were led to believe that there was no placebo control group. The participants later completed the 5-Dimensional Altered States of Consciousness Rating Scale, which measures changes in conscious experience.
Results: There was considerable individual variation in the placebo effects; many participants reported no changes while others showed effects with magnitudes typically associated with moderate or high doses of psilocybin. In addition, the majority (61%) of participants verbally reported some effect of the drug. Several stated that they saw the paintings on the walls “move” or “reshape” themselves, others felt “heavy…as if gravity [had] a stronger hold”, and one had a “come down” before another “wave” hit her.
Conclusion: Understanding how context and expectations promote psychedelic-like effects, even without the drug, will help researchers to isolate drug effects and clinicians to maximise their therapeutic potential.
…In the second sample, before the debriefing, we asked participants to guess whether they had taken a psychedelic, a placebo, or whether they were uncertain. Overall, 35% reported being certain they had taken a placebo, 12% were certain that they had taken a psychedelic, and the rest (53%) were uncertain. In the first sample, we did not ask this question, but the same number of people spontaneously reported being certain that they had taken a psychedelic drug. During the debriefing, when we revealed the placebo nature of the study, many participants appeared shocked. Several gasped and started laughing. One stated, “It’s very funny!”, and another replied, “It’s sad!” One of the participants who had sat with a group near the paintings throughout the study asked, “So we were all sober and just watching these paintings for 45 minutes‽”
[“This is a remarkable study, and probably the most elaborate placebo ever reported. But how well did the trick work? The authors say that after they revealed the truth, some of the participants expressed shock. However, 35% of them said they were”certain" they had taken a placebo when quizzed just before the debriefing. Only 12% were “certain” that they’d taken a real psychedelic drug, which suggests that the deception was only partially successful.
Some of the participants did report very strong effects on a questionnaire of ‘psychedelic effects’. However, I noticed that the effects reported tended to be the more abstract kind, such as “insight” and “bliss”. In terms of actual hallucinogenic effects like ‘complex imagery’ and ‘elementary imagery’ (ie. seeing things), no participants reported effects equal to even a low dose of LSD, let alone a stronger dose. See the rather confusing Figure 2 for details." —Neuroskeptic]
Recently popular sub-perceptual doses of psychedelic substances such as truffles, referred to as microdosing, allegedly have multiple beneficial effects including creativity and problem solving performance, potentially through targeting serotonergic 5-HT2A receptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults.
Methods: During a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking, and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were manifested.
Results: We found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected.
Conclusion: While this study provides quantitative support for the cognitive enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.
“A systematic study of microdosing psychedelics”, (2018-12-10):
The phenomenon of ‘microdosing’, that is, regular ingestion of very small quantities of psychedelic substances, has seen a rapid explosion of popularity in recent years. Individuals who microdose report minimal acute effects from these substances yet claim a range of long-term general health and wellbeing benefits. There have been no published empirical studies of microdosing and the current legal and bureaucratic climate makes direct empirical investigation of the effects of psychedelics difficult.
In Study One we conducted a systematic, observational investigation of individuals who microdose. We tracked the experiences of 98 microdosing participants, who provided daily ratings of psychological functioning over a six week period. 63 of these additionally completed a battery of psychometric measures tapping mood, attention, wellbeing, mystical experiences, personality, creativity, and sense of agency, at baseline and at completion of the study. Analyses of daily ratings revealed a general increase in reported psychological functioning across all measures on dosing days but limited evidence of residual effects on following days. Analyses of pre and post study measures revealed reductions in reported levels of depression and stress; lower levels of distractibility; increased absorption; and increased neuroticism.
To better understand these findings, in Study Two we investigated pre-existing beliefs and expectations about the effects of microdosing in a sample of 263 naïve and experienced microdosers, so as to gauge expectancy bias. All participants believed that microdosing would have large and wide-ranging benefits in contrast to the limited outcomes reported by actual microdosers. Notably, the effects believed most likely to change were unrelated to the observed pattern of reported outcomes.
The current results suggest that dose controlled empirical research on the impacts of microdosing on mental health and attentional capabilities are needed.
Psychedelic microdosing describes the ingestion of near-threshold perceptible doses of classic psychedelic substances. Anecdotal reports and observational studies suggest that microdosing may promote positive mood and well-being, but recent placebo-controlled studies failed to find compelling evidence for this.
The present study collected web-based mental health and related data using a prospective (before, during and after) design. Individuals planning a weekly microdosing regimen completed surveys at strategic timepoints, spanning a core 4-week test period. 81 participants completed the primary study endpoint. Results revealed increased self-reported psychological well-being, emotional stability and reductions in state anxiety and depressive symptoms at the four-week primary endpoint, plus increases in psychological resilience, social connectedness, agreeableness, nature relatedness and aspects of psychological flexibility. However, positive expectancy scores at baseline predicted subsequent improvements in well-being, suggestive of a substantial placebo response. This study highlights a role for positive expectancy in predicting positive outcomes following psychedelic microdosing and cautions against zealous inferences on its putative therapeutic value.
…Due to the pragmatic challenges of doing so via an online observational study, the present study did not include a placebo control condition. We did, however, employ a prospective, naturalistic design that included baseline sampling of expectations about possible outcomes from the impending microdosing. Well-being, state anxiety and depressive symptom scores were measured weekly on five occasions (pre-dosing at baseline to week 4 of the microdosing regimen) in order to track time-dependent changes. Neuroticism/emotional stability was measured pre-dosing at baseline and post-dosing at week 4 only. It was predicted that well-being and emotional stability would be increased, and that depression and anxiety scores would be decreased, at the key-endpoint (4 weeks) compared with baseline. Capitalising on the nature of the prospective design, we also predicted that baseline positive expectations about microdosing would be related to any subsequent improvements in well-being, depressive symptoms and anxiety scores. Finally, exploratory analyses were performed to assess pre-post changes in a range of secondary psychological outcomes of interest.
…Expectancy effect on main outcome change scores: One-tailed partial correlations using Pearson coefficient were employed in order to investigate the effects of baseline expectations on endpoint change scores (endpoint—baseline) for the primary outcome variables (well-being, depressive symptoms and anxiety), whilst controlling for the corresponding baseline scores. In line with our main hypothesis, expectations for well-being improvement were statistically-significantly associated with change scores in well-being (r = 0.275 [d = −0.57], p = 0.007), depressive symptoms (r = −0.263 [d = −0.54], p = 0.009) and anxiety (r = −0.220 [d = −0.45], p = 0.025). These results indicate that baseline expectations were predictive of mental health change at the study endpoint.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814527/: “Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers”, Anya K. Bershad, Scott T. Schepers, Michael P. Bremmer, Royce Lee, Harriet de Wit
Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect.
This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date.
All psychological outcomes improved statistically-significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no statistically-significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but statistically-significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind.
The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.
…It is worth noting that the current study was designed to protect blinding integrity by including placebos for the microdose group as well, administering the microdose capsules on different days of the week and by including the half-half group. The 3-arm design can be seen as a strength in this regard, adding ambiguity and thus strengthening blinding. Illustrative of the integrity of the blind, we received several emails from participants in the PL group who were in disbelief after opening their unused envelopes containing unused capsules after the conclusion of the study:
- “I counted the number of cut blotters I had in the left overs: they are 8…so you must be right… Which is incredible […] Some days during the test were really, really focused and colours more vivid. This sensation was really new to me”.
- “I have just checked the remaining envelopes and it appears that I was indeed taking placebos throughout the trial. I’m quite astonished […] It seems I was able to generate a powerful ‘altered consciousness’ experience based only the expectation around the possibility of a microdose”.
- “An empty pill with strong belief/intentions makes nearly everything. You put spirituality into an empty pill here…wow!”
eLife digest: Psychedelic psychotherapy, therapy enhanced with psychedelic drugs such as LSD or psilocybin (the active ingredient of ‘magic mushrooms’), has been suggested to improve psychological well-being. For this reason, trials on psychedelic therapy for the treatment of depression, addiction and other conditions are ongoing. Recently, ‘microdosing’—a way of administering psychedelics that involves taking about 10% of a recreational dose 2 or 3× per week—has gained popularity. Unlike taking large doses of psychedelics, microdosing does not induce hallucinations, but anecdotal reports suggest that it yields similar benefits as psychedelic therapy.
A key feature of modern medicine are ‘placebo control’ studies that compare two groups of patients: one that takes a drug and another that takes inactive pills, known as placebos. Crucially, neither group knows whether they are taking drug or placebo. This control ensures that observed effects are due to the drug itself and not to unrelated psychological causes. For example, in trials of mood medicines, participants often expect to feel happier, which in itself improves their mood even when taking a placebo. This is known as the placebo effect.
Restrictive drug policies make placebo-controlled studies on psychedelics difficult and expensive, in particular for microdosing, which involves taking psychedelics over a longer time period. To overcome this problem, Szigeti et al. developed a new citizen-science approach, where microdosers implemented their own placebo control based on online instructions. The advantages are the low cost and the ability to recruit participants globally. The experiment was completed by 191 microdosers, making it the largest placebo-controlled study on psychedelics to-date, for a fraction of the cost of an equivalent clinical study.
The trial examined whether psychedelic microdosing can improve cognitive function and psychological well-being. The team found that microdosing statistically-significantly increased a number of psychological measures, such as well-being and life satisfaction. However, participants taking placebo also improved: there were no statistically-significant differences between the two groups. The findings confirmed positive anecdotes about microdosing improving people’s moods, but at the same time show that taking empty capsules, knowing they might be microdoses, have the same benefits. This result suggests that the observed benefits are not caused by the microdose, but rather by psychological expectations.
The study’s innovative ‘do-it-yourself’ approach to placebo control may serve as a template for future citizen science studies on other popular phenomena where positive expectations and social factors could play a role, such as cannabidiol (CBD) oils, nootropics and nutrition.
2016-caudevilla-2.pdf: “Results of an international drug testing service for cryptomarket users”, (2016-09-01; ):
Introduction: User surveys indicate that expectations of higher drug purity are a key reason for cryptomarket use. In 2014–2015, Spain’s NGO Energy Control conducted a 1-year pilot project to provide a testing service to drug users using the Transnational European Drug Information (TEDI) guidelines. In this paper, we present content and purity data from the trial.
Methods: 219 samples were analyzed by gas chromatography associated with mass spectrometry (GC/MS). Users were asked to report what substance they allegedly purchased.
Results: 40 different advertised substances were reported, although 77.6% were common recreational drugs (cocaine, MDMA, amphetamines, LSD, ketamine, cannabis). In 200 samples (91.3%), the main result of analysis matched the advertised substance. Where the advertised compound was detected, purity levels (m ± SD) were: cocaine 71.6 ± 19.4%; (crystal) 88.3 ± 1.4%; MDMA (pills) 133.3 ± 38.4 mg; Amphetamine (speed) 51.3 ± 33.9%; LSD 123.6 ± 40.5 μg; Cannabis resin THC: 16.5 ± 7.5% CBD: 3.4 ± 1.5%; Ketamine 71.3 ± 38.4%. 39.8% of cocaine samples contained the adulterant levamisole (11.6 ± 8%). No adulterants were found in and LSD samples.
Discussion: The largest collection of test results from drug samples delivered from cryptomarkets are reported in this study. Most substances contained the advertised ingredient and most samples were of high purity. The representativeness of these results is unknown.
[Keywords: cryptomarkets, drug markets, purity, adulterants, drug checking, drug trend monitoring]
[See also Arce 2020.]
2016-gouwe.pdf: “Purity, adulteration and price of drugs bought online versus offline in the Netherlands”, Daan Gouwe, Tibor M. Brunt, Margriet Laar, Peggy Pol
“Psychedelics and Mental Health: A Population Study”, (2013-04-11):
The classical serotonergic psychedelics LSD, psilocybin, mescaline are not known to cause brain damage and are regarded as non-addictive. Clinical studies do not suggest that psychedelics cause long-term mental health problems. Psychedelics have been used in the Americas for thousands of years. Over 30 million people currently living in the US have used LSD, psilocybin, or mescaline.
To evaluate the association between the lifetime use of psychedelics and current mental health in the adult population.
Data drawn from years 2001 to 2004 of the National Survey on Drug Use and Health consisted of 130,152 respondents, randomly selected to be representative of the adult population in the United States. Standardized screening measures for past year mental health included serious psychological distress (K6 scale), mental health treatment (inpatient, outpatient, medication, needed but did not receive), symptoms of eight psychiatric disorders (panic disorder, major depressive episode, mania, social phobia, general anxiety disorder, agoraphobia, posttraumatic stress disorder, and non-affective psychosis), and seven specific symptoms of non-affective psychosis. We calculated weighted odds ratios by multivariate logistic regression controlling for a range of sociodemographic variables, use of illicit drugs, risk taking behavior, and exposure to traumatic events.
21,967 respondents (13.4% weighted) reported lifetime psychedelic use. There were no psychedelics (LSD, psilocybin, mescaline, peyote), or past year use of LSD and increased rate of any of the mental health outcomes. Rather, in several cases psychedelic use was associated with lower rate of mental health problems.associations between lifetime use of any psychedelics, lifetime use of specific
We did not find use of psychedelics to be an independent risk factor for mental health problems.
1994-doj-sentencing.pdf: “FY1995 Federal Sentencing Statistics by State, District and Circuit”, U. S. Sentencing Commission
Persistent forms of nondual awareness, enlightenment, mystical experience, and so forth (Persistent Non-Symbolic Experience) have been reported since antiquity. Though sporadic research has been performed on them, the research reported here represents the initial report from the first larger scale cognitive psychology study of this population.
Method: Assessment of the subjective experience of fifty adult participants reporting persistent non-symbolic experience was undertaken using 6–12 hour semi-structured interviews and evaluated using thematic analysis. Additional assessment was performed using psychometric measures, physiological measurement, and experimentation.
Results: Five core, consistent categories of change were uncovered: sense-of-self, cognition, emotion, perception, and memory. Participants’ reports formed clusters in which the types of change in each of these categories were consistent. Multiple clusters were uncovered that formed a range of possible experiences. The variety of these experiences and their underlying categories may inform the debate between constructivist, common core, and participatory theorists.
…Over the course of a week, his father died followed very rapidly by his sister. He was also going through a major issue with one of his children. Over dinner I asked him about his internal state, which he reported as deeply peaceful and positive despite everything that was happening. Having known that the participant was bringing his longtime girlfriend, I’d taken an associate researcher with me to the meeting to independently collect the observations from her. My fellow researcher isolated the participant’s girlfriend at the bar and interviewed her about any signs of stress that the participant might be exhibiting. I casually asked the same questions to the participant as we continued our dinner conversation. Their answers couldn’t have been more different. While the participant reported no stress, his partner had been observing many telltale signs: he wasn’t sleeping well, his appetite was off, his mood was noticeably different, his muscles were much tenser than normal, his sex drive was reduced, his health was suffering, and so forth…It was not uncommon for participants to state that they had gained increased bodily awareness upon their transition into PNSE. I arranged and observed private yoga sessions with a series of participants as part of a larger inquiry into their bodily awareness. During these sessions it became clear that participants believed they were far more aware of their body than they actually were…Many participants discussed the thought, just after their transition to PNSE, that they would have to go to work and explain the difference in themselves to co-workers. They went on to describe a puzzled drive home after a full day of work when no one seemed to notice anything different about them. Quite a few chose to never discuss the change that had occurred in them with their families and friends and stated that no one seemed to notice much of a difference.
There was also a progressively decreasing sense of agency. In the final stage, Location 4, he reports: “These participants reported having no sense of agency or any ability to make a decision. It felt as if life was simply unfolding and they were watching the process happen. Severe memory deficits were common in these participants, including the inability to recall scheduled events that were not regular and ongoing.” And yet, almost all of the subjects reported it as a positive experience. The subjects, at whatever point they were in the scale, were often completely certain about the nature of the experience: “PNSE was often accompanied by a tremendous sense of certainty that participants were experiencing a ‘deeper’ or ‘more true’ reality. As time passed, this often increased in strength.” They also tended to be dogmatic about their PNSE being the real thing (whichever location they were at) and descriptions of other people’s different PNSEs as not the real thing. Another way to say “completely certain” is “unable to doubt”.