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Psychedelic Assisted Therapy for Treating Addiction – Part 2

Psychedelic Assisted Therapy for Treating Addiction – Part 2

Introduction

In recent years, there has been an increasing interest in the potential of psychedelic therapy as a novel approach for the treatment of addiction. This interest stems from a growing body of research exploring the therapeutic effects of psychedelic substances on addictive behaviors, particularly psilocybin and LSD. In his past seminar titled “Euphoria: The New Science of Addiction and Psychedelic Therapy,” Dr. Rayyan Zafar, a prominent researcher in the field, delves into the key insights and findings spanning from observational studies, clinical trials, and historical investigations with psychedelics in addiction treatment. Dr. Zafar sheds light on the historical context, scientific progress, and prospects of psychedelic therapy in addiction treatment. This blog post aims to summarize and analyze the key takeaways from Dr. Zafar’s seminar, providing readers with a deeper understanding of the evolving landscape of addiction treatment and the role of psychedelic therapy within it.

Key Takeaways from “Euphoria: The New Science of Addiction and Psychedelic Therapy”

 

Comprehensive Review of Psychedelic Therapy in Addiction Treatment


Dr. Zafar’s past seminar offered an in-depth examination of the potential of psychedelic therapy in treating addiction, drawing on a diverse range of research sources. The exploration begins with historical studies dating back to the mid to late 1900s, shedding light on the origins of psychedelic research and its developmental trajectory. Both classic (e.g. psilocybin, LSD, and DMT) and non-classical psychedelics (e.g. 6-MeO-DMT, ketamine, and MDMA) were discussed but due to the limited scope of this article, only the classic ones, psilocybin and LSD, will be highlighted. 

The first realization of the powerful effect of LSD on mood and cognition in 1943 presumably marked the beginning of a modern era in which psychedelic drugs could be used to treat certain mental and behavioral conditions. From the 1940s and early 1970s, classic psychedelics were actively researched in humans as both a pharmacological tool to understand its effects on the mind and brain and as a therapeutics. Collectively, LSD was seen as a promising treatment for numerous serious mental health disorders such as depression, alcoholism, and other substance use disorders (Hofman, 1980). Furthermore, it has a favorable safety profile and had profound short-term psychological effects (Krebs). This led to a potential breakthrough in the treatment of various mental illnesses, including different forms of drug addiction (Belouin). 

Between the late 1950s and early 1970s, approximately 40,000 patients worldwide suffering from various mental disorders, including substance use disorders, received treatment with psychedelics such as LSD, mescaline, and psilocybin, are documented over 1000 publications (Grinspoon). A key finding was that psychedelics are well-tolerated and induce a low risk of adverse side events (online event).

A controlled study investigating LSD’s efficacy in adjunction to psychotherapy in treating heroin addiction was influential. It was revealed that 33% of 36 participants in the treatment group (n= 73) maintained a abstinence after one year compared to the control group with a mere 5% success rate. However, only 5% maintain complete abstinence after the fulfilling the treatment program (Savage, 1973). Furthermore, a meta-analysis collected data about LSD in alcoholism from six randomized controlled trials that were published in the 1960s with over 500 participants and showed that LSD doubled the odds that patients would be abstinent at first follow-up, as defined by (OR = 2.07). Yet, this was not seen after a year (Krebs). 

Even though there is quite a large amount of historical data showing a positive trend toward the therapeutic role of psychedelics in addiction treatment, the evidence from these studies remains inconclusive due to methodological inconsistencies. More specifically, these inconsistencies encompassed deficiencies in study design, such as the lack of proper controls, blinding, follow-up protocols, statistical analyses, and the utilization of validated assessments, as evaluated through contemporary research standards (Rucker). 

Groundbreaking Investigations into Addiction Treatment with Psychedelic-assisted Therapy

The widespread use of psychedelics in the 1960s fueled a counterculture movement, prompting a political backlash and leading to increased regulatory controls by the FDA. This culminated in the establishment of the Controlled Substances Act (CSA) in 1970 under Richard Nixon, effectively halting psychedelic research (Belouin). However, efforts to explore the therapeutic potential of psychedelics resumed in the 1990s with renewed scientific interest and advanced research methodologies (Belouin; Zafar).

Dr. Zafar provided an overview of the latest findings from these investigations, illuminating the favorable prospects of psychedelics in addiction recovery. Ongoing clinical trials exploring the potential therapeutic role of psychedelics in addiction cover a diverse spectrum of substances and addiction types, ranging from alcohol and tobacco to methamphetamine and gambling addiction. Due to the limited scope of this article, only psilocybin in alcohol and tobacco will be highlighted. These trials aim to expand upon initial findings and set the stage for larger-scale studies that would ultimately secure regulatory approval. 

The promising results of earlier research on psychedelics and alcohol addiction have prompted a modern replication open-label study examining psilocybin-assisted treatment for alcohol dependence (Bogenschutz et el., 2015). In the little sneak preview of last week, the study of psilocybin in conjunction with Motivational Enhancement Therapy (MET) was discussed. The figure illustrates the change in percent drinking days and percent heavy drinking days. The blue line in the graph represent the % of drinking days while the red line represent the % heavy drinking days. After the first administration with psilocybin, both percent drinking and heavy drinking days were statistically significant lower than baseline in all the follow-up points. 

To explore the relationship between the intensity of the psilocybin-induced experience with changes in drinking behavior, the acute effects of psilocybin were measured by the Mystical Experiences Questionnaire (MEQ). It was also found to correlate with changes in drinking behavior, craving, and self-efficacy (Bogenschutz, 2015). 

The mystical experiences induced by psilocybin are characterized by immediate sensations of unity, sacredness, a sense of understanding beyond ordinary knowledge, positive mood, transcendence of notions of space and time, and an inability to adequately describe the experience (e.g., ineffability; Griffiths, 2006). These dimensions seem to be common across ages, cultures, ethnicities, and genders (online seminar Johnson). The hallmark of the mystical experience lies in the profound sense of being influenced by forces greater than oneself, often accompanied by intense emotions, sparking enduring and transformative changes in one’s life (Miller). 

To build upon the findings of the study of Bogenschutz et al. (2015), the research group investigated psilocybin in a so-called phase 2 double-blind randomized clinical trial (Bogenschutz, 2022). On one hand, it was observed that the psilocybin group had lower percentage  in heavy drinking days and mean daily alcohol consumption (number of standard drinks per day) compared to the group that was given diphenhydramine as a control. On the other hand, the percentage of drinking days was not statistically reduced (29 in psilocybin group vs 43 in control groups). However, important limitations need to be pointed out. There were some methodological issues that could lead to a higher risk of making incorrect inferences about the data.This study is currently undergoing replication in larger phase III trials across multiple centers, advancing toward creating more data regarding the efficacy of the psychedelic drug and potential marketing authorization for this indication (Zafar).

The effects of psilocybin have also been investigated in conjunction with CBT for the treatment of tobacco addiction. In this open-label study, individuals were given two to three moderate to high doses (20 and 30 mg/70kg) of psilocybin (Johnson, 2017). Results based on urinary and breath analyses showed that 60% of the group did not smoke after one year of follow-up. This is a seemingly big difference compared to the 35% of what is usually observed in traditional tobacco treatment paradigms (Cahill, 2014). In the acknowledgment of the lack of drawing definitive conclusions based on open-label studies and the lack of a control group, a randomized comparative efficacy study has been performed and the results remain yet to be published. 

Future Applications with Neuroimaging Techniques

Various neuroimaging techniques are able to provide insights into the neurobiological mechanisms of psychedelic therapy and how these relate to clinical outcomes in the treatment of addiction. These techniques include functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT) scans and enable researchers to map changes in both brain activity and connectivity, offering a deeper understanding of addiction mechanisms and treatment outcomes. Despite the relative scarcity of literature on the neurobiological mechanisms of psychedelics in addiction, recent studies have shed light on potential pathways such as reward, inhibitory control, and stress (Hayes).

Neuroimaging studies are invaluable in identifying biomarkers associated with substance dependence. These biomarkers serve as an objective measurement of bodily activity and, thus, aim to elucidate the mechanisms and conditions under which treatments prove effective. For instance, PET and SPECT, have enabled researchers to delve into the molecular dynamics of addiction within the living human brain. These methods have unveiled specific neuroreceptor biomarkers associated with different subclasses of addiction. Take, for example, the findings regarding dopamine receptors in alcohol and stimulant use disorder (Nutt et al., 2015), opioid receptors in cocaine (Gorelick et al., 2005), and opioid dependence (Williams et al., 2007). Such insights have not only paved the way for a deeper understanding of addiction pathology but also presented novel targets for therapeutic intervention. 

Furthermore, by utilizing radioligands, neurotransmitter release studies have offered valuable insights into the dynamics of neurotransmission in addiction. The dopamine system has been widely implicated in addiction theory (Nutt, 2015; Zafar). In addiction, specifically, a blunted dopamine release in a brain region called the nucleus accumbens has been observed after a drug was given. When investigating the effect of psychedelics on addiction, it has been suggested that there is a potential link between psychedelics and dopamine release (Martin et al., 2024; Vollenweider et al. 1999). Yet, so far neurochemical studies have been done in non-humans and futher research is warranted (Nutt, 2015).

Dr. Zafar discusses that advanced multimodal neuroimaging techniques are necessary to directly assess the effects of psychedelic therapy on neurotransmission and brain function in individuals with addiction. For example, multimodal imaging studies combining PET and fMRI have proposed that psychedelic therapy may lead to increases in endogenous dopamine levels in addiction disorders, potentially reflecting improved brain function and treatment outcomes. One of his future scientific endeavors will investigate using fMRI and EEG to investigate differences between pre-and post-administration with psilocybin. Ultimately, these advances ultimately pave the way for more personalized and efficient approaches to address substance dependence (Moeller).

Addressing Challenges and Knowledge Gaps

While the collective data on psychedelics and addiction suggests a positive trend toward reducing substance use, and cravings, and fostering abstinence compared to conventional treatments, several critical knowledge gaps and controversies persist, necessitating further exploration and clarification. Besides the limitations associated with naturalistic, observational, open-label, and animal studies, we will highlight some knowledge gaps that are critical to address when exploring psychedelics and addiction. Indeed, when one door closes, another hundred seem to open.

One of the main remaining questions is: “What mediates the long-term effects of psychedelics?”

The enduring psychological and behavioral changes observed after psychedelic use may be partly influenced by the immediate, often subjectively positive effects of 5-HT2A receptor agonists, which are occasionally described as mystical or transcendent (Bogenschutz 2015; Calder; Griffiths 2006, 2008, 2011; Johnson 2017; Rothberg; Tap; Yaden). Griffiths (2011) even found that psilocybin can affect the Big Five personality traits, typically considered stable, by increasing openness. Similar associations between greater mystical experiences and improved outcomes were observed in psychedelic-assisted therapy (PAT) for smoking cessation (Johnson, 2017). The findings suggest that psilocybin-assisted treatment has lasting impacts beyond the drug’s immediate effects, with participants ranking their psilocybin experiences as some of the most personally significant and spiritually impactful, correlating with higher smoking cessation rates (Johnson 2017).

While these studies did not explicitly focus on spirituality, the findings raise questions about its role in the effects of psychedelic drugs on addiction. The emotion of awe is suggested as a crucial mechanism driving mystical experiences during psychedelic-assisted psychotherapy (Kan). Awe fosters feelings of interconnectedness and unity, which are central to the transformative effects of psychedelic therapy (Griffiths, 2008). Data indicates that more profound mystical experiences increase the likelihood of smoking cessation (Johnson, 2017). However, not all mystical experiences lead to lasting change, and individuals may return to their previous state. Future randomized, placebo-controlled clinical trials with multiple follow-up assessments are necessary to establish causality and determine the clinical significance of these mechanisms.

Another remaining question concerns the use of a particular therapeutic framework when psychedelics are administered to individuals with addiction. The literature is clear that psychotherapy plays a crucial role in addiction treatment, but it remains unknown what the right amount and particular type of psychotherapeutic intervention and relapse prevention is best. Some studies indicate that group therapy alongside psychedelic use may enhance group connectedness and interpersonal understanding, potentially promoting prosocial behavior (Ponomarenko). While mystical experiences often foster profound connections with others and the universe, solo settings remain prevalent, though both solo and group therapies have shown no significant differences in mental health perceptions (Byrne).

Another remaining question is “How do psychedelics impact the neural circuits implicated in addiction?” Answers to these questions can give insights into how to optimize the development of psychedelic-assisted therapies. Psychedelics may disrupt networks associated with addiction and enhance connectivity across the brain, fostering neuroplasticity and facilitating the relearning of behaviors (Carhart-Harris; Calder; Nutt 2023; online event; Tap). However, understanding these neuroplasticity mechanisms remains limited, with studies primarily conducted on animal models and cell lines (Calder)

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Conclusion 

In conclusion, the field of addiction treatment is undergoing a profound transformation with the exploration of psychedelic therapy. Early research indicates that psychedelics like psilocybin and LSD show a positive trend in reducing addictive behaviors, supported by both historical and somewhat by modern clinical trials. By leveraging cutting-edge techniques, neuroimaging studies, researchers can elucidate the underlying mechanisms of psychedelic interventions and tailor treatments to individual needs. Despite the promising data, methodological inconsistencies and knowledge gaps remain, necessitating further rigorous research. Looking ahead, the future of psychedelics and addiction holds some promise, fueled by groundbreaking research, innovative treatment modalities, and a growing understanding of the complex interplay between neuroscience, psychology, and pharmacology. 

By Gwendolyn Drossaert


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References

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  31. Online event
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Trip: Psychedelics, Alienation, and Change

Trip: Psychedelics, Alienation, and Change. Tao Lin. Random House USA. ISBN: 9781101974513

After discovering the works of Terence McKenna, Lin embarks on a journey of personal discovery that aids his recovery from addiction, changes his world view and leads him to ask big questions such as: Why do we make art? Is the world made of language? What happens when we die? And is the imagination more real than the universe?

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Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study

Abstract

Background and aims: Ibogaine is an indole alkaloid used in rituals of the African Bwiti tribe. It is also used in non-medical settings to treat addiction. However, ibogaine has been linked to several deaths, mainly due to cardiac events called torsades des pointes preceded by QTc prolongation as well as other safety concerns. This study aimed to evaluate the cardiac, cerebellar and psychomimetic safety of ibogaine in patients with opioid use disorder.

Design: A descriptive open-label observational study.

Setting: Department of psychiatry in a university medical center, the Netherlands.

Participants: Patients with opioid use disorder (n = 14) on opioid maintenance treatment with a lasting wish for abstinence, who failed to reach abstinence with standard care.

Intervention and measurements: After conversion to morphine-sulphate, a single dose of ibogaine-HCl 10 mg/kg was administered and patients were monitored at regular intervals for at least 24 hours assessing QTc, blood pressure and heart rate, scale for the assessment and rating of ataxia (SARA) to assess cerebellar side effects and the delirium observation scale (DOS) to assess psychomimetic effects.

Findings: The maximum QTc (Fridericia) prolongation was on average 95ms (range 29-146ms). Fifty percent of subjects reached a QTc of over 500ms during the observation period. In six out 14 subjects prolongation above 450ms lasted beyond 24 hours after ingestion of ibogaine. No torsades des pointes were observed. Severe transient ataxia with inability to walk without support was seen in all patients. Withdrawal and psychomimetic effects were mostly well-tolerated and manageable (11/14 did not return to morphine within 24 hours, DOS scores remained below threshold).

Conclusions: This open-label observational study found that ibogaine treatment of patients with opioid use disorder can induce a clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia.

Knuijver, T., Schellekens, A., Belgers, M., Donders, R., van Oosteren, T., Kramers, K., & Verkes, R. (2022). Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study. Addiction (Abingdon, England), 117(1), 118–128. https://doi.org/10.1111/add.15448

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Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes

Abstract

Mescaline is a naturally occurring psychoactive alkaloid that has been used as a sacrament by Indigenous populations in spiritual ritual and healing ceremonies for millennia. Despite promising early preliminary research and favorable anecdotal reports, there is limited research investigating mescaline’s psychotherapeutic potential. We administered an anonymous online questionnaire to adults (N = 452) reporting use of mescaline in naturalistic settings about mental health benefits attributed to mescaline. We assessed respondents’ self-reported improvements in depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol and drug use disorders (AUD and DUD). Of the respondents reporting histories of these clinical conditions, most (68-86%) reported subjective improvement following their most memorable mescaline experience. Respondents who reported an improvement in their psychiatric conditions reported significantly higher ratings of acute psychological factors including mystical-type, psychological insight, and ego dissolution effects compared to those who did not report improvements (Cohen’s d range 0.7 – 1.5). Many respondents (35-50%) rated the mescaline experience as the single or top five most spiritually significant or meaningful experience(s) of their lives. Acute experiences of psychological insight during their mescaline experience were associated with increased odds of reporting improvement in depression, anxiety, AUD and DUD. Additional research is needed to corroborate these preliminary findings and to rigorously examine the efficacy of mescaline for psychiatric treatment in controlled, longitudinal clinical trials.

Agin-Liebes, G., Haas, T. F., Lancelotta, R., Uthaug, M. V., Ramaekers, J. G., & Davis, A. K. (2021). Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes. ACS pharmacology & translational science, 4(2), 543–552. https://doi.org/10.1021/acsptsci.1c00018

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Clinical and biological predictors of psychedelic response in the treatment of psychiatric and addictive disorders: A systematic review

Abstract

Background: The use of psychedelic treatments has shown very promising results in some psychiatric and addictive disorders, but not all patients achieved a response.

Aim: The aim of this review is to explore the clinical and biological factors which could predict the response to psychedelics in psychiatric and addictive disorders.

Methods: A systematic research was performed on MEDLINE, PsycInfo, Web of science, and Scopus databases from January 1990 to May 2020. All studies investigating the predictive factors of response to psychedelics regardless of psychiatric or addictive disorders, were included.

Results: Twenty studies investigating addictive disorder, treatment-resistant depression, obsessive-compulsive disorder and depressive and anxiety symptoms in patients with life-threatening cancer were included in this review. We found that, in all indications, the main predictive factor of response to psychedelics is the intensity of the acute psychedelic experience. Indeed, we found this factor for alcohol and tobacco use disorders, treatment-resistant depression, and anxiety and depressive symptoms in patients with life-threatening cancer, but not for obsessive-compulsive disorder.

Conclusion: The intensity of the acute psychedelic experience was the main predicting factor of response. The action mechanism of this experience was not clear, but some hypotheses could be made, such as a modulation of serotoninergic system by 5-HT2A receptors agonism, a modulation of the default mode network (DMN) with an acute modular disintegration of the DMN followed by a re-integration of this network with a normal functioning, or an anti-inflammatory effect of this treatment.

Romeo, B., Hermand, M., Pétillion, A., Karila, L., & Benyamina, A. (2021). Clinical and biological predictors of psychedelic response in the treatment of psychiatric and addictive disorders: A systematic review. Journal of psychiatric research, 137, 273–282. https://doi.org/10.1016/j.jpsychires.2021.03.002

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First study of safety and tolerability of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in patients with alcohol use disorder

Abstract

Background: 3,4-methylenedioxymethamphetamine (MDMA) therapy has qualities that make it potentially well suited for patients with addictions, but this has never been explored in a research study. We present data from the Bristol Imperial MDMA in Alcoholism (BIMA) study. This is the first MDMA addiction study, an open-label safety and tolerability proof-of-concept study investigating the potential role for MDMA therapy in treating patients with alcohol use disorder (AUD).

Aims: This study aimed to assess if MDMA-assisted psychotherapy can be delivered safely and can be tolerated by patients with AUD post detoxification. Outcomes regarding drinking behaviour, quality of life and psychosocial functioning were evaluated.

Methods: Fourteen patients with AUD completed a community alcohol detoxification and received an eight-week course of recovery-based therapy. Participants received two sessions with MDMA (187.5 mg each session). Psychological support was provided before, during and after each session. Safety and tolerability were assessed alongside psychological and physiological outcome measures. Alcohol use behaviour, mental well-being and functioning data were collected for nine months after alcohol detoxification.

Results: MDMA treatment was well tolerated by all participants. No unexpected adverse events were observed. Psychosocial functioning improved across the cohort. Regarding alcohol use, at nine months post detox, the average units of alcohol consumption by participants was 18.7 units per week compared to 130.6 units per week before the detox. This compares favourably to a previous observational study (the ‘Outcomes’ study) by the same team with a similar population of people with AUD.

Conclusions: This study provides preliminary support for the safety and tolerability of a novel intervention for AUD post detox. Further trials to examine better the therapeutic potential of this approach are now indicated.

Sessa, B., Higbed, L., O’Brien, S., Durant, C., Sakal, C., Titheradge, D., Williams, T. M., Rose-Morris, A., Brew-Girard, E., Burrows, S., Wiseman, C., Wilson, S., Rickard, J., & Nutt, D. J. (2021). First study of safety and tolerability of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in patients with alcohol use disorder. Journal of psychopharmacology (Oxford, England), 35(4), 375–383. https://doi.org/10.1177/0269881121991792

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What is the clinical evidence on psilocybin for the treatment of psychiatric disorders? A systematic review

Abstract

Background: Psilocybin is a predominant agonist of 5HT1A and 5HT2A/C receptors and was first isolated in 1958, shortly before it became a controlled substance. Research on the potential therapeutic effects of this compound has recently re-emerged alongside what is being addressed as a psychedelic renaissance.

Methods: In this paper we performed a systematic review of the clinical trials conducted so far regarding the therapeutic effects of psilocybin on psychiatric disorders. The eligibility criteria included clinical trials that assessed psilocybin’s potential therapeutic effects on patients with psychiatric disorders. Nine hundred seven articles were found and screened in regard to the title, from which 94 were screened through abstract and 9 met the eligibility criteria and were included.

Results: The papers published focused on 3 disorders: depression, obsessive-compulsive disorder (OCD) and substance use disorder (namely tobacco and alcohol). Psilocybin has shown a relatively safe profile and very promising results, with reductions found on most of the psychiatric rating scales’ scores. Research on depression showed the most solid evidence, supported by 3 randomized controlled trials. Studies on OCD and substance use disorder showed more limitations due to their open-label design.

Conclusions: Altogether, the results from the studies reviewed in this paper suggest a substantial therapeutic potential. This calls for further research to confirm the results observed so far and further explain the underlying mechanisms.

Castro Santos, H., & Gama Marques, J. (2021). What is the clinical evidence on psilocybin for the treatment of psychiatric disorders? A systematic review. Porto biomedical journal, 6(1), e128. https://doi.org/10.1097/j.pbj.0000000000000128

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Within-treatment changes in a novel addiction treatment program using traditional Amazonian medicine

Abstract

Aims: The therapeutic use of psychedelics is regaining scientific momentum, but similarly psychoactive ethnobotanical substances have a long history of medical (and other) uses in indigenous contexts. Here we aimed to evaluate patient outcomes in a residential addiction treatment center that employs a novel combination of Western and traditional Amazonian methods.

Methods: The study was observational, with repeated measures applied throughout treatment. All tests were administered in the center, which is located in Tarapoto, Peru. Data were collected between 2014 and 2015, and the study sample consisted of 36 male inpatients who were motivated to seek treatment and who entered into treatment voluntarily. Around 58% of the sample was from South America, 28% from Europe, and the remaining 14% from North America. We primarily employed repeated measures on a psychological test battery administered throughout treatment, measuring perceived stress, craving frequency, mental illness symptoms, spiritual well-being, and physical and emotional health. Addiction severity was measured on intake, and neuropsychological performance was assessed in a subsample from intake to at least 2 months into treatment.

Results: Statistically significant and clinically positive changes were found across all repeated measures. These changes appeared early in the treatment and were maintained over time. Significant improvements were also found for neuropsychological functioning.

Conclusion: These results provide evidence for treatment safety in a highly novel addiction treatment setting, while also suggesting positive therapeutic effects.

O’Shaughnessy, D. M., Berlowitz, I., Rodd, R., Sarnyai, Z., & Quirk, F. (2021). Within-treatment changes in a novel addiction treatment program using traditional Amazonian medicine. Therapeutic advances in psychopharmacology, 11, 2045125320986634. https://doi.org/10.1177/2045125320986634

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Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

Abstract

Classical psychedelics, primarily psilocybin and lysergic acid diethylamide (LSD), have been used and extensively studied in Western medicine as part of substance-assisted psychotherapy in the 1950s and 1960s. Modern clinical research is currently gaining momentum and provides new evidence for the safety and efficacy of classical psychedelics (primarily psilocybin, but also LSD and ayahuasca) in the treatment of different psychiatric conditions, including substance use and mood disorders.In this review article, we outline common pathological mechanisms of substance use disorders (SUD) and unipolar depression. Next, the current literature on the effects of psychedelics is summarized in order to generate hypotheses regarding their potential therapeutic mechanisms of action in treating these psychiatric conditions. Finally, we review and discuss clinical trials published since 2011 investigating the effects of psychedelics in SUD and depression.While results from those modern clinical trials are promising, most of them do not meet the methodological requirements to allow firm conclusions on the clinical efficacy of psychedelics. Larger, blinded, randomized controlled trials (RCT) with clearly defined patient groups and well-defined primary endpoints are needed. Additionally, the therapeutic mechanisms of classical psychedelics are currently unknown. This review presents hypotheses derived from preclinical and human studies that need to be tested in future trials to better understand the clinical potential of psychedelic substances in modern psychiatry.

Mertens, L. J., & Preller, K. H. (2021). Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders. Pharmacopsychiatry, 54(4), 176–190. https://doi.org/10.1055/a-1341-1907

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Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy

Abstract

Mounting evidence supports the serotonin 2A receptor agonist psilocybin as a psychiatric pharmacotherapy. Little research has experimentally examined how session “set and setting” impacts subjective and therapeutic effects. We analyzed the effects of the musical genre played during sessions of a psilocybin study for tobacco smoking cessation. Participants (N = 10) received psilocybin (20-30 mg/70 kg) in two sessions, each with a different musical genre (Western classical versus overtone-based), with the order counterbalanced. Participants chose one genre for a third session (30 mg/70 kg). Mystical experiences scores tended to be higher in overtone-based sessions than in Western classical sessions. Six of ten participants chose the overtone-based music for a third session. Biologically confirmed smoking abstinence was similar based on musical choice, with a slight benefit for participants choosing the overtone-based playlist (66.7% versus 50%). These data call into question whether Western classical music typically used in psychedelic therapy holds a unique benefit. Broadly, we call for experimentally examining session components toward optimizing psychedelic therapeutic protocols.

Strickland, J. C., Garcia-Romeu, A., & Johnson, M. W. (2020). Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy. ACS pharmacology & translational science, 4(2), 472–478. https://doi.org/10.1021/acsptsci.0c00187

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