OPEN Foundation

Personality

Long-term effects of psychedelic drugs: A systematic review

Abstract

Research into the basic effects and therapeutic applications of psychedelic drugs has grown considerably in recent years. Yet, pressing questions remain regarding the substances’ lasting effects. Although individual studies have begun monitoring sustained changes, no study to-date has synthesized this information. Therefore, this systematic review aims to fill this important gap in the literature by synthesizing results from 34 contemporary experimental studies which included classic psychedelics, human subjects, and follow-up latencies of at least two weeks. The bulk of this work was published in the last five years, with psilocybin being the most frequently administered drug. Enduring changes in personality/attitudes, depression, spirituality, anxiety, wellbeing, substance misuse, meditative practices, and mindfulness were documented. Mystical experiences, connectedness, emotional breakthrough, and increased neural entropy were related to these long-term changes in psychological functioning. Finally, with proper screening, preparation, supervision, and integration, limited aversive side effects were noted by study participants. Future researchers should focus on including larger and more diverse samples, lengthier longitudinal designs, stronger control conditions, and standardized dosages.

Aday, J. S., Mitzkovitz, C. M., Bloesch, E. K., Davoli, C. C., & Davis, A. K. (2020). Long-term effects of psychedelic drugs: A systematic review. Neuroscience & Biobehavioral Reviews., 10.1016/j.neubiorev.2020.03.017
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The Psychedelic Renaissance and Its Forensic Implications

Abstract

Recent years have seen a renaissance of research into the use of psychedelic compounds to address various psychiatric conditions. The study of these substances went dormant in 1970 when the United States government passed the Controlled Substances Act, which categorized lysergic acid diethylamide, commonly known as LSD or acid, as a Schedule I drug. The rise of psychedelics in research settings raises questions regarding their risks outside of clinical trials. The available data on the impact of psychedelic use on interpersonal violence and other criminal behavior remain scant. Although Timothy Leary’s work of the 1960s failed to clearly demonstrate a reduction in criminal recidivism with psychedelic-assisted psychotherapy, recent studies suggest that the use of psychedelics may reduce individuals’ risk of interpersonal violence. Forensic psychiatrists should be aware of this research, as well as the role that psychedelics may play in various forensic assessments. This article summarizes basic information that the forensic practitioner should know about psychedelic substances, including their various effects and proposed mechanism of action; describes historical and recent research into psychedelics and criminal behavior; and offers evaluators a practical means by which to assess individuals’ psychedelic use in forensic contexts.

Holoyda, B. (2020). The Psychedelic Renaissance and Its Forensic Implications. The journal of the American Academy of Psychiatry and the Law48(1), 87-97., 10.29158/JAAPL.003917-20
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Use of Benefit Enhancement Strategies among 5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) Users: Associations with Mystical, Challenging, and Enduring Effects.

Abstract

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a potent, fast-acting psychedelic. Anecdotal reports from 5-MeO-DMT users suggest that they employ a variety of benefit enhancement (BE) strategies aimed to increase positive effects and decrease any potential challenging effects of the substance, but no empirical study has investigated this claim. We examined the prevalence of BE strategy use using secondary data from a survey of 5-MeO-DMT users (n = 515; Mage = 35.4, SD = 11.7; Male = 79%; White/Caucasian = 86%). Results indicated that BE strategy use was common in this sample. As a secondary aim, we assessed whether the use of BE strategies was associated with acute subjective (i.e., mystical-type, challenging) and persisting effects of 5-MeO-DMT among a subset of respondents who reported using 5-MeO-DMT once in their lifetime (n = 116). Results showed that the use of several BE strategies were associated with significantly more intense mystical-type effects and enduring beliefs about the personal meaning and spiritual significance of their experience, and some BE strategies were associated with less intense or challenging experiences. Data suggests that BE strategies are commonly used, and that the use of BE strategies may be associated with increases in positive mystical-type and enduring effects. The causal influence of BE strategies on acute/persisting effects of 5-MeO-DMT should be examined in longitudinal research.

Lancelotta, R. L., & Davis, A. K. (2020). Use of benefit enhancement strategies among 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) users: Associations with mystical, challenging, and enduring effects. Journal of Psychoactive Drugs, 1-9.,10.1080/02791072.2020.1737763
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Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression

Abstract

BACKGROUND:

Psilocybin has shown promise as a treatment for depression but its therapeutic mechanisms are not properly understood. In contrast to the presumed actions of antidepressants, we recently found increased amygdala responsiveness to fearful faces one day after open-label treatment with psilocybin (25 mg) in 19 patients with treatment-resistant depression, which correlated with treatment efficacy.

AIMS:

Aiming to further unravel the therapeutic mechanisms of psilocybin, the present study extends this basic activation analysis. We hypothesised changed amygdala functional connectivity, more precisely decreased amygdala-ventromedial prefrontal cortex functional connectivity, during face processing after treatment with psilocybin.

METHODS:

Psychophysiological interaction analyses were conducted on functional magnetic resonance imaging data from a classic face/emotion perception task, with the bilateral amygdala and ventromedial prefrontal cortex time-series as physiological regressors. Average parameter estimates (beta weights) of significant clusters were correlated with clinical outcomes at one week.

RESULTS:

Results showed decreased ventromedial prefrontal cortex-right amygdala functional connectivity during face processing post- (versus pre-) treatment; this decrease was associated with levels of rumination at one week. This effect was driven by connectivity changes in response to fearful and neutral (but not happy) faces. Independent whole-brain analyses also revealed a post-treatment increase in functional connectivity between the amygdala and ventromedial prefrontal cortex to occipital-parietal cortices during face processing.

CONCLUSION:

These results are consistent with the idea that psilocybin therapy revives emotional responsiveness on a neural and psychological level, which may be a key treatment mechanism for psychedelic therapy. Future larger placebo-controlled studies are needed to examine the replicability of the current findings.

Mertens, L. J., Wall, M. B., Roseman, L., Demetriou, L., Nutt, D. J., & Carhart-Harris, R. L. (2020). Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression. Journal of Psychopharmacology, 10.1177/0269881119895520
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Replication and extension of a model predicting response to psilocybin

Abstract

BACKGROUND:

Recent research demonstrated the potential of psychedelic drugs as treatment for depression and death-related anxiety and as an enhancement for well-being. While generally positive, responses to psychedelic drugs can vary according to traits, setting, and mental state (set) before and during ingestion. Most earlier models explain minimal response variation, primarily related to dosage and trust, but a recent study found that states of surrender and preoccupation at the time of ingestion explained substantial variance in mystical and adverse psilocybin experiences.

OBJECTIVES:

The current study sought to replicate the previous model, extend the model with additional predictors, and examine the role of mystical experience on positive change.

METHOD:

A hierarchical regression model was created with crowdsourced retrospective data from 183 individuals who had self-administered psilocybin in the past year. Scales explored mental states before, during, and after psilocybin ingestion, relying on open-ended memory prompts at each juncture to trigger recollections. Controlled drug administration was not employed.

RESULTS:

This study replicated the previous model, finding a state of surrender before ingestion a key predictor of optimal experience and preoccupation a key predictor of adverse experience. Additional predictors added to the explanatory power for optimal and adverse experience. The model supported the importance of mystical experiences to long-term change.

CONCLUSION:

Mental states of surrender or preoccupation at the time of ingestion explain variance in mystical or adverse psilocybin experiences, and mystical experiences relate to long-term positive change. The capacity to recognize this optimal preparatory mental state may benefit therapeutic use of psilocybin in clinical settings.

Russ, S. L., Carhart-Harris, R. L., Maruyama, G., & Elliott, M. S. (2019). Replication and extension of a model predicting response to psilocybin. Psychopharmacology, 1-10., 10.1007/s00213-019-05279-z
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Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers

Abstract

BACKGROUND:

Numerous anecdotal reports suggest that repeated use of very low doses of lysergic acid diethylamide (LSD), known as microdosing, improves mood and cognitive function. These effects are consistent both with the known actions of LSD on serotonin receptors and with limited evidence that higher doses of LSD (100-200 μg) positively bias emotion processing. Yet, the effects of such subthreshold doses of LSD have not been tested in a controlled laboratory setting. As a first step, we examined the effects of single very low doses of LSD (0-26 μg) on mood and behavior in healthy volunteers under double-blind conditions.

METHODS:

Healthy young adults (N = 20) attended 4 laboratory sessions during which they received 0 (placebo), 6.5, 13, or 26 μg of LSD in randomized order at 1-week intervals. During expected peak drug effect, they completed mood questionnaires and behavioral tasks assessing emotion processing and cognition. Cardiovascular measures and body temperature were also assessed.

RESULTS:

LSD produced dose-related subjective effects across the 3 doses (6.5, 13, and 26 μg). At the highest dose, the drug also increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content. Other mood measures, cognition, and physiological measures were unaffected.

CONCLUSIONS:

Single microdoses of LSD produced orderly dose-related subjective effects in healthy volunteers. These findings indicate that a threshold dose of 13 μg of LSD might be used safely in an investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.

Bershad, A. K., Schepers, S. T., Bremmer, M. P., Lee, R., & de Wit, H. (2019). Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers. Biological Psychiatry., 10.1016/j.biopsych.2019.05.019
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Narrative identity, rationality, and microdosing classic psychedelics

Abstract

BACKGROUND:

Microdosing involves ingesting a small dose of a classic psychedelic (e.g., LSD and psilocybin) at regular intervals for prolonged periods. The practice is said to reduce anxiety, improve mood, and offer several creative and practical benefits to users. Using the narrative identity theoretical framework, our aim was to explore the experiences of those who microdosed classic psychedelics. Specifically, we sought to understand how and why they began microdosing and how they made sense of their actions in the context of their conventional lives.

METHODS:

To understand the experiences of those who microdose classic psychedelics, we rely on data collected from semi-structured interviews with 30 people who had microdosed.

RESULTS:

Participants saw themselves as conventional citizens who microdosed for rational and instrumental purposes. They emphasized the rationality of microdosing by discussing (1) the practicality of their procurement and administration processes, (2) the connection between their microdosing practice and their general awareness in health and wellness, and (3) the benefits of the practice.

CONCLUSION:

Participants described their microdosing in the context of embracing traditional middle-class values. This created social distance between themselves and those who use drugs recreationally. While people who use drugs recreationally typically construct boundaries by distancing themselves from symbolic others (i.e., “crackheads,” “meth heads,” “junkies”), microdosers constructed boundaries by emphasizing connections to conventional citizens who embrace middle-class values. This connection to conventional citizens allows them to normalize their drug use and facilitates persistence.

Webb, M., Copes, H., & Hendricks, P. S. (2019). Narrative identity, rationality, and microdosing classic psychedelics. International Journal of Drug Policy70, 33-39., 10.1016/j.drugpo.2019.04.013
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Embracing Neurodiversity in Psychedelic Science: A Mixed-Methods Inquiry into the MDMA Experiences of Autistic Adults

Abstract

This exploratory inquiry analyzed subjective experiences autistic adults reported after they took the drug 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy, in nonclinical settings. Using a secure, globally available website, this study collected data from participants in 13 countries who were experienced with MDMA (n = 100). A subset of survey respondents (n = 24) were then invited to participate in qualitative interviews. The researcher applied thematic content analysis of interview transcripts to create a comprehensive account of emergent themes. MDMA has well-documented acute effects that promote pro-social attitudes such as caring and trust in neurotypical, or typically developing, populations. Findings from this study suggested that MDMA-assisted therapy may be an effective catalyst in autistic adults for intra- and interpersonal change. In addition, participants reported accounts of lasting transformation and healing from conditions such as trauma and social anxiety that are common in autistic populations. No participants reported long-term adverse outcomes as a result of using MDMA/ecstasy. Qualitative findings support a case for future clinical trials of MDMA-assisted therapy with autistic adults who present with social adaptability challenges.

Danforth, A. L. (2019). Embracing neurodiversity in psychedelic science: A mixed-methods inquiry into the MDMA experiences of autistic adults. Journal of psychoactive drugs51(2), 146-154., 10.1080/02791072.2019.1587116
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Recreational use of psychedelics is associated with elevated personality trait openness: Exploration of associations with brain serotonin markers

Abstract

BACKGROUND:

Recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. The understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. However, recent studies in both healthy and clinical populations suggest a role for personality changes.

AIM:

To test support for some of these plausible mechanisms we evaluated (cross-sectional) associations between recreational use of psychedelics and 3,4-methylene-dioxymethamphetamine (MDMA) and (a) personality measures and (b) key markers of cerebral serotonergic signalling (serotonin transporter and serotonin-2A-receptor binding).

METHODS:

In 10 psychedelic-preferring recreational users, 14 MDMA-preferring users and 21 non-using controls, personality was assessed using the ‘big five’ instrument Revised NEO Personality Inventory (NEO-PI-R). Frontal serotonin transporter and serotonin-2A-receptor binding potentials were quantified using [11C]DASB and [18F]altanserin positron emission tomography, respectively.

RESULTS:

Of the five NEO-PI-R traits, only openness to experience scores differed between the three groups; psychedelic-preferring recreational users showing higher openness to experience scores when compared with both MDMA-preferring users and controls. Openness to experience scores were positively associated with lifetime number of psychedelic exposures, and among all MDMA-preferring user/psychedelic-preferring recreational user individuals, frontal serotonin transporter binding – but not frontal serotonin-2A-receptor binding – was positively associated with openness to experience.

CONCLUSION:

Our findings from this cross-sectional study support increasing evidence of a positive association between psychedelic experiences and openness to experience, and (a) expands this to the context of ‘recreational’ psychedelics use, and (b) links serotonergic neurotransmission to openness to experience. A modulation of personality induced by psychedelic experiences may have important therapeutic implications via its impact on peoples’ value systems, cognitive flexibility, and individual and social behaviour.

Erritzoe, D., Smith, J., Fisher, P. M., Carhart-Harris, R., Frokjaer, V. G., & Knudsen, G. M. (2019). Recreational use of psychedelics is associated with elevated personality trait openness: Exploration of associations with brain serotonin markers. Journal of Psychopharmacology., 10.1177/0269881119827891
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Ayahuasca and Public Health: Health Status, Psychosocial Well-Being, Lifestyle, and Coping Strategies in a Large Sample of Ritual Ayahuasca Users

Assessing the health status of ayahuasca users has been challenging due to the limitations involved in randomized clinical trials and psychometric approaches. The main objective of this study is the implementation of an approach based on public health indicators. We developed a self-administered questionnaire that was administered to long-term ayahuasca users around Spain. The questionnaire was administrated face-to-face to participants (n = 380) in places where ayahuasca ceremonies were occurring. Public health indicators were compared with Spanish normative data, and intergroup analyses were conducted. Long-term ayahuasca use was associated with higher positive perception of health or with a healthy lifestyle, among other outcomes. Fifty-six percent of the sample reported reducing their use of prescription drugs due to ayahuasca use. Participants who used ayahuasca more than 100 times scored higher in personal values measures. The main conclusion of this study is that a respectful and controlled use of hallucinogenic/psychedelic drugs taken in communitarian settings can be incorporated into modern society with benefits for public health. This new approach, based on the use of health indicators that were not used in previous ayahuasca studies, offers relevant information about the impact of long-term exposure to ayahuasca on public health.

Ona, G., Kohek, M., Massaguer, T., Gomariz, A., Jiménez, D. F., Dos Santos, R. G., … & Bouso, J. C. (2019). Ayahuasca and Public Health: Health Status, Psychosocial Well-Being, Lifestyle, and Coping Strategies in a Large Sample of Ritual Ayahuasca Users. Journal of psychoactive drugs, 1-11., 10.1080/02791072.2019.1567961
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30 April - Q&A with Rick Strassman

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