Psychoactives, Volume 3, Issue 2 (June 2024) – 5 articles

Rationale: Psychedelic research re-emerged from a period of suppression into the so-called psychedelic renaissance. In parallel, most media reporting has shifted from the overstatement of the risks of psychedelics to overly positive hype. As the empirical evidence is more equivocal than frequently portrayed, the conclusions about the effectiveness of psychedelics should be considered preliminary. Poor science communication about psychedelics’ therapeutic potential may lead potential participants or patients to feel misled and policy decisions to be misinformed. An evidence-informed characterization of their risks and benefits is needed. Objectives: This article assesses the state of psychedelic research for treating depression and the effect sizes of psychedelics on therapeutic outcomes, the risk of bias, and the prevalence of adverse effects. We review research on the risks and benefits of psychedelics and discuss how the following depression treatments have shown decreasing effect sizes over time: (1) cognitive behavioral therapy, (2) mindfulness interventions, (3) selective serotonin reuptake inhibitors, and (4) ketamine. We speculate that a similar trend may occur for psychedelic treatments. Results and conclusions: It is likely that larger and better-controlled psychedelic trials will demonstrate smaller effect sizes that are more comparable to other conventional and emerging treatments for mood disorders. Clear science communication is critical for setting public expectations and psychedelic policy. With this evidence-based assessment, we aim to cut through the misinformation about the benefits, risks, and future prospects of psychedelic treatments. Full article

We explored the intricate interplay of biological, social, and psychological factors contributing to substance use disorder (SUD) and co-occurring psychiatric symptoms. Drug misuse is a global concern, with increasing prevalence rates affecting mental well-being and safety. The spectrum of SUD includes polysubstance users, posing challenges for treatment and associated health outcomes. Various psychoactive substances like cannabis, hallucinogens, opioids, and stimulants impact addiction vulnerability, with marijuana being widely used globally. Gender differences in SUD prevalence have narrowed, with women escalating drug consumption rapidly once initiated. Age disparities in substance use highlight regional variations among adolescents. Comorbidities with psychiatric symptoms are common, with mood and anxiety disorders frequently observed. This study aimed to analyze factors influencing SUD development and maintenance to inform prevention strategies and treatment recommendations. By conducting a systematic search of databases, sixty articles were reviewed, revealing diverse methodologies and geographic locations. Biological factors, including neurotransmitter systems like endocannabinoid and dopaminergic systems, play a significant role in addiction. Genetic and neurobiological factors contribute to cannabis addiction susceptibility. Social factors such as childhood experiences and parenting styles influence substance use behaviors. Psychological factors like personality traits and mental health conditions interact with SUD development. Understanding these multifaceted interactions is crucial for designing effective interventions to address the complexities of SUD and co-occurring psychiatric symptoms. Full article

(1) Background: Intraperitoneal injections of the endogenous N-acyl amino acid N-Oleoyl alanine (OlAla) effectively reduces both the affective and somatic responses produced by opioid withdrawal in preclinical models. To increase the translational appeal of OlAla in clinical drug applications, the current experiments tested whether oral OlAla pretreatment also attenuates opioid withdrawal in rats. (2) Methods: In Experiment 1, to assess its impact on affective withdrawal behavior, OlAla (0, 5, 20 mg/kg) was orally administered during the conditioning phase of an acute naloxone-precipitated morphine withdrawal conditioned place avoidance task. In Experiment 2, to assess its impact on somatic withdrawal behavior, OlAla (5–80 mg/kg) was orally administered prior to naloxone-precipitated withdrawal from chronic heroin exposure. (3) Results: Pretreatment with oral OlAla at the higher (20 mg/kg), but not lower (5 mg/kg) dose, reduced the establishment of an acute morphine withdrawal-induced conditioned place aversion. Instead, the lower dose of oral OlAla (5 mg/kg) reduced heroin withdrawal-induced abdominal contractions and diarrhea, whereas higher doses were without effect. (4) Conclusions: The results suggest a dose-dependent reduction of opioid withdrawal responses by orally administered OlAla, and further highlight the potential utility of this compound for opioid withdrawal in clinical populations. Full article

Background: In recent years, there has been a growing interest in the therapeutic potential of classical psychedelics like ayahuasca for mental health improvement. Naturalistic studies at ayahuasca retreats have shown (short-term) improvements in mental well-being but understanding the psychological mechanisms is crucial. We are interested in psychological processes such as resilience, self-compassion, and personality traits. Additionally, it is unclear whether changes are solely due to ayahuasca or influenced by the social setting. To address this, a control group participating in a breathwork session, similar to ayahuasca retreats, was included. Methods: In this observational study, individuals who attended an ayahuasca retreat (n = 69) and individuals who participated in a breathwork session (n = 30) completed an online survey one week before (baseline) and one, six, and twelve weeks after they entered the retreat/session. The survey included a series of questionnaires, i.e., the World Health Organisation-Five Well-Being Index, 14-item Resilience Scale, Self-Compassion Scale–Short Form, and Big Five Inventory-10. A linear mixed model (LMM) was used to analyze the outcome data. Results: It was shown that well-being, resilience, and self-compassion increased and remained stable over 12 weeks compared to baseline, regardless of group (ayahuasca or breathwork). Older participants generally reported higher resilience and self-compassion. Self-compassion was also higher in the ayahuasca group overall. Neuroticism decreased in both groups, with lower scores in the ayahuasca group. Agreeableness increased over time, also not influenced by group membership, while there were no changes in extraversion, conscientiousness, or openness. Discussion: Both interventions improved well-being, aligning with prior research. Importantly, this study unveils a novel finding: both interventions enhance resilience and self-compassion for up to three months, offering promise for conditions marked by low well-being, resilience, and self-compassion like depression and anxiety-related disorders. While acknowledging its limitations (e.g., self-selected sample, no specific information of the ayahuasca brew or the breathwork technique), it emphasizes the need for controlled studies with control groups, attention to social contexts in research on these interventions, and to assess other variables like depth of altered states of consciousness that might explain improvement in psychological processes and wellbeing. Full article

A set of interventions that can produce altered states of consciousness (ASC) have shown utility in the treatment of substance misuse. In this review, we examine addiction-related outcomes associated with three common interventions that produce ASCs: psychedelic-assisted psychotherapy (PP), Transcendental Meditation (TM) and hypnotherapy (HT). While procedurally distinct, all three interventions are associated with some common phenomenological, psychological, and neurobiological features, indicating some possible convergent mechanisms of action. Along with addiction and mental health outcomes, these common features are reviewed, and their impact on substance misuse is discussed. While our review highlights some mixed findings and methodological issues, results indicate that PP and TM are associated with significant improvements in substance misuse, alongside improvements in emotional, cognitive and social functioning, behavior-change motivation, sense of self-identity, and meaning. In contrast, and despite its broader acceptance, HT has been associated with mixed and minimal results with respect to substance misuse treatment. Authors identify key research gaps in the role of ASC interventions in addiction and outline a set of promising future research directions. Full article