Top Academic Articles

Opening to Awe: Psychedelic‐Assisted Self‐Transcendence and Positive Adult Development

Recent studies implicate the use of psychedelic substances in the treatment of psychiatric conditions. However, this literature also suggests that the psychedelics may have utility in the promotion of positive adult development. Accordingly, this paper outlines a study exploring this premise. An online sample (n=684) of psychedelic users and non-users (age range: 18–24 to 75–84; median=25–34) was recruited. Conditional process analysis was used to assess whether the relationship between psychedelic use and two facets of adult development, adjustment and growth, would be mediated by openness to experience, awe-proneness, and mystical experiences, and whether these relationships would be moderated by drug-use reflection/integration. Results show that the direct relationship between psychedelic use and growth was moderated by drug-use reflection/integration. In addition, the indirect relationship between psychedelic use and adjustment was mediated through awe-proneness, while the indirect relationships between psychedelic use and growth were mediated via awe- proneness and openness to experience; drug-use reflection/integration moderated these mediated relationships. In addition, drug-use reflection/integration directly predicted openness, awe-proneness, and growth. These findings suggest that, when used with self-expansive intentions and actively refected upon and integrated post use, psychedelics may augment positive adult development.

MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study

The success of modern medicine creates a growing population of those suffering from life-threatening illnesses (LTI) who often experience anxiety, depression, and existential distress. We present a novel approach; investigating MDMA-assisted psychotherapy for the treatment of anxiety in people with an LTI. Participants with anxiety from an LTI were randomized in a double-blind study to receive MDMA (125 mg, n = 13) or placebo (n = 5) in combination with two 8-h psychotherapy sessions. The primary outcome was change in State-Trait Anxiety Inventory (STAI) Trait scores from baseline to one month post the second experimental session. After unblinding, participants in the MDMA group had one open-label MDMA session and placebo participants crossed over to receive three open-label MDMA sessions. Additional follow-up assessments occurred six and twelve months after a participant’s last experimental session. At the primary endpoint, the MDMA group had a greater mean (SD) reduction in STAI-Trait scores, − 23.5 (13.2), indicating less anxiety, compared to placebo group, − 8.8 (14.7); results did not reach a significant group difference (p = .056). Hedges’ g between-group effect size was 1.03 (95% CI: − 5.25, 7.31). Overall, MDMA was well-tolerated in this sample. These preliminary findings can inform development of larger clinical trials to further examine MDMA-assisted psychotherapy as a novel approach to treat individuals with LTI-related anxiety.

A systematic literature review of clinical trials and therapeutic applications of ibogaine

Background: Iboga and its primary alkaloids, ibogaine and noribogaine, have been of interest to researchers and practitioners, mainly due to their putative efficacy in treating substance use disorders (SUDs). For many SUDs, still no effective pharmacotherapies exist. Distinct psychoactive and somatic effects of the iboga alkaloids set them apart from classic hallucinogens like LSD, mescaline, and psilocybin. Aims: The study team performed this systematic review focusing on clinical data and therapeutic interventions involving ibogaine and noribogaine. Methods: The team conducted a search for all publications up to December 7, 2020, using PubMed and Embase following PRISMA guidelines. Results: In total, we identified 743 records. In this review, we consider 24 studies, which included 705 individuals receiving ibogaine or noribogaine. This review includes two randomized, double-blind, controlled clinical trials, one double-blind controlled clinical trial, 17 open-label studies or case series (including observational or retrospective studies), three case reports, and one retrospective survey. The published data suggest that ibogaine is an effective therapeutic intervention within the context of SUDs, reducing withdrawal symptoms and craving. Data also point toward a beneficial impact on depressive and trauma-related psychological symptoms. However, studies have reported severe medical complications and deaths, which seem to be associated with neuro- and cardiotoxic effects of ibogaine. Two of these fatalities were described in the 24 studies included in this review. Conclusion: Treatment of SUDs and persisting comorbidities requires innovative treatment approaches. Rapid-onset therapies such as the application of ibogaine may offer novel treatment opportunities for specific individuals. Rigorous study designs within medical settings are necessary to warrant safe application, monitoring, and, possibly, medical intervention.

Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression

Abstract Rationale: Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations. Aim: Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian–authoritarian political perspective in patients with treatment-resistant depression (TRD). Methods: This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian–authoritarian political perspective in patients with moderate to severe TRD (n=7) versus age-matched non-treated healthy control subjects (n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7–12 months after the second dosing session. Nature relatedness and libertarian–authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnaire (PPQ-5), respectively. Results: Nature relatedness significantly increased (t(6)=−4.242, p=0.003) and authoritarianism significantly decreased (t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7–12 months post-dosing, nature relatedness remained significantly increased (t(5)=−2.707, p=0.021) and authoritarianism remained decreased at trend level (t(5)=−1.811, p=0.065). No differences were found on either measure for the non-treated healthy control subjects. Conclusions: This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small study, the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation.

Some distorted thoughts about ketamine as a psychedelic and a novel hypothesis based on NMDA receptor-mediated synaptic plasticity

Ketamine, a channel blocking NMDA receptor antagonist, is used off-label for its psychedelic effects, which may arise from a combination of several inter-related actions. Firstly, reductions of the contribution of NMDA receptors to afferent information from external and internal sensory inputs may distort sensations and their processing in higher brain centres. Secondly, reductions of NMDA receptor-mediated excitation of GABAergic interneurons can result in glutamatergic overactivity. Thirdly, limbic cortical disinhibition may indirectly enhance dopaminergic and serotonergic activity. Fourthly, inhibition of NMDA receptor mediated synaptic plasticity, such as short-term potentiation (STP) and long-term potentiation (LTP), could lead to distorted memories. Here, for the first time, we compared quantitatively the effects of ketamine on STP and LTP. We report that ketamine inhibits STP in a double sigmoidal fashion with low (40 nM) and high (5.6 μM) IC50 values. In contrast, ketamine inhibits LTP in a single sigmoidal manner (IC50 value ∼ 15 μM). A GluN2D-subunit preferring NMDA receptor antagonist, UBP145, has a similar pharmacological profile. We propose that the psychedelic effects of ketamine may involve the inhibition of STP and, potentially, associated forms of working memory. This article is part of the Special Issue entitled ‘Psychedelics: New Doors, Altered Perceptions’. Keywords: GluN2D subunit; Ketamine; LTP; Long-term potentiation; Memory; NMDA receptors; PCP; Phencyclidine; Psychedelics; STP; Short-term potentiation; Working memory.

DMT Models the Near-Death Experience

Near-death experiences (NDEs) are complex subjective experiences, which have been previously associated with the psychedelic experience and more specifically with the experience induced by the potent serotonergic, N,N-Dimethyltryptamine (DMT). Potential similarities between both subjective states have been noted previously, including the subjective feeling of transcending one’s body and entering an alternative realm, perceiving and communicating with sentient ‘entities’ and themes related to death and dying. In this within-subjects placebo-controled study we aimed to test the similarities between the DMT state and NDEs, by administering DMT and placebo to 13 healthy participants, who then completed a validated and widely used measure of NDEs. Results revealed significant increases in phenomenological features associated with the NDE, following DMT administration compared to placebo. Also, we found significant relationships between the NDE scores and DMT-induced ego-dissolution and mystical-type experiences, as well as a significant association between NDE scores and baseline trait ‘absorption’ and delusional ideation measured at baseline. Furthermore, we found a significant overlap in nearly all of the NDE phenomenological features when comparing DMT-induced NDEs with a matched group of ‘actual’ NDE experiencers. These results reveal a striking similarity between these states that warrants further investigation. “I’d be scared”. “Scared of what?” “Scared of dying, I guess. Of falling into the void”. “They say you fly when you die”. (Feature film: ‘Enter the Void’).

A systematic study of microdosing psychedelics

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.

The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption

Background/aim: 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in several plants and in high concentrations in Bufo alvarius toad venom. Synthetic, toad, and plant-sourced 5-MeO-DMT are used for spiritual and recreational purposes and may have psychotherapeutic effects. However, the use of 5-MeO-DMT is not well understood. Therefore, we examined patterns of use, motivations for consumption, subjective effects, and potential benefits and consequences associated with 5-MeO-DMT use. Methods: Using internet-based advertisements, 515 respondents (Mage=35.4. SD=11.7; male=79%; White/Caucasian=86%; United States resident=42%) completed a web-based survey. Results: Most respondents consumed 5-MeO-DMT infrequently (<once/year), for spiritual exploration, and had used less than four times in their lifetime. The majority (average of 90%) reported moderate-to-strong mystical-type experiences (Mintensity=3.64, SD=1.11; range 0–5; e.g., ineffability, timelessness, awe/amazement, experience of pure being/awareness), and relatively fewer (average of 37%) experienced very slight challenging experiences (Mintensity=0.95, SD=0.91; range 0–5; e.g., anxiousness, fear). Less than half (39%) reported repeated consumption during the same session, and very few reported drug craving/desire (8%), or legal (1%), medical (1%), or psychiatric (1%) problems related to use. Furthermore, of those who reported being diagnosed with psychiatric disorders, the majority reported improvements in symptoms following 5-MeO-DMT use, including improvements related to post-traumatic stress disorder (79%), depression (77%), anxiety (69%), and alcoholism (66%) or drug use disorder (60%). Conclusion: Findings suggest that 5-MeO-DMT is used infrequently, predominantly for spiritual exploration, has low potential for addiction, and might have psychotherapeutic effects. Future research should examine the safety and pharmacokinetics of 5-MeO-DMT administration in humans using rigorous experimental designs.

Neural correlates of the LSD experience revealed by multimodal neuroimaging

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD’s marked effects on the visual cortex did not significantly correlate with the drug’s other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of “ego-dissolution” and “altered meaning,” implying the importance of this particular circuit for the maintenance of “self” or “ego” and its processing of “meaning.” Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.