Cognitive functioning associated with acute and subacute effects of classic psychedelics and MDMA - a systematic review and meta-analysis.

Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders. Several studies have been carried out to assess potential long-term effects of a regular use on cognition, delivering distinct results for psychedelics and MDMA. However, to date knowledge is scarce on cognitive performance during acute effects of those substances. In this systematic review and meta-analysis, we investigate how cognitive functioning is affected by psychedelics and MDMA during the acute drug effects and the sub-acute ("afterglow") window. Our quantitative analyses suggest that acute cognitive performance is differentially affected by psychedelics when compared to MDMA: psychedelics impair attention and executive function, whereas MDMA primarily affects memory, leaving executive functions and attention unaffected. Our qualitative analyses reveal that executive functioning and creativity may be increased during a window of at least 24 h after the acute effects of psychedelics have subsided, whereas no such results have been observed for MDMA. Our findings may contribute to inform recommendations on harm reduction for recreational settings and to help fostering differential approaches for the use of psychedelics and MDMA within a therapeutic framework.

Psychiatric and non-psychiatric patients during the midst of Covid-19: Pandemic distress, psychosis and the belief in conspiracy theories.

BACKGROUND: The COVID-19 pandemic was associated with increased levels of psychological distress in the general population, at the same time providing a perfect breeding ground for conspiracy beliefs. Psychiatric patients are considered as a population with an increased vulnerability for stressful events, and conspiracy beliefs show overlaps with paranoid ideations. The aim of the present study was to investigate if psychiatric patients experienced higher levels of pandemic distress than non-psychiatric patients, if they were more prone to conspiracy beliefs and if pandemic distress as well as other mental health variables were associated with believing in conspiracy theories. METHODS: Indicators for mental health (pandemic distress, depressive symptoms, general anxiety symptoms, perceived stress) and indicators for believing in conspiracy theories were assessed within psychiatric (n = 73) and non-psychiatric patients (n = 29) during the midst of the pandemic. RESULTS: Psychiatric patients reported higher levels of pandemic distress than non-psychiatric patients. Conspiracy measurements correlated positively with pandemic distress, but not with anxiety and depression. No differences were found between psychiatric patients with or without psychotic disorder and non-psychiatric patients in regard to conspiracy measurements. CONCLUSION: Our findings suggest a higher susceptibility of psychiatric patients to pandemic distress, but not an increased level of believing in conspiracy theories. The common notion that people suffering from psychosis are more likely to believe in conspiracy theories was not supported. Furthermore, distress caused by a specific event and not anxiety per se seems to be related to the degree of conspiracy beliefs.

The psychedelic afterglow phenomenon: a systematic review of subacute effects of classic serotonergic psychedelics.

Background: Classic serotonergic psychedelics have anecdotally been reported to show a characteristic pattern of subacute effects that persist after the acute effects of the substance have subsided. These transient effects, sometimes labeled as the 'psychedelic afterglow', have been suggested to be associated with enhanced effectiveness of psychotherapeutic interventions in the subacute period. Objectives: This systematic review provides an overview of subacute effects of psychedelics. Methods: Electronic databases (MEDLINE, Web of Science Core Collection) were searched for studies that assessed the effects of psychedelics (LSD, psilocybin, DMT, 5-MeO-DMT, mescaline, or ayahuasca) on psychological outcome measures and subacute adverse effects in human adults between 1950 and August 2021, occurring between 1 day and 1 month after drug use. Results: Forty-eight studies including a total number of 1,774 participants were eligible for review. Taken together, the following subacute effects were observed: reductions in different psychopathological symptoms; increases in wellbeing, mood, mindfulness, social measures, spirituality, and positive behavioral changes; mixed changes in personality/values/attitudes, and creativity/flexibility. Subacute adverse effects comprised a wide range of complaints, including headaches, sleep disturbances, and individual cases of increased psychological distress. Discussion: Results support narrative reports of a subacute psychedelic 'afterglow' phenomenon comprising potentially beneficial changes in the perception of self, others, and the environment. Subacute adverse events were mild to severe, and no serious adverse events were reported. Many studies, however, lacked a standardized assessment of adverse effects. Future studies are needed to investigate the role of possible moderator variables and to reveal if and how positive effects from the subacute window may consolidate into long-term mental health benefits.

Dose-response relationships of LSD-induced subjective experiences in humans.

Lysergic acid diethylamide (LSD) is a potent classic serotonergic psychedelic, which facilitates a variety of altered states of consciousness. Here we present the first meta-analysis establishing dose-response relationship estimates of the altered states of consciousness induced by LSD. Data extracted from articles identified by a systematic literature review following PRISMA guidelines were obtained from the Altered States Database. The psychometric data comprised ratings of subjective effects from standardized and validated questionnaires: the Altered States of Consciousness Rating Scale (5D-ASC, 11-ASC) and the Mystical Experience Questionnaire (MEQ30). We performed meta-regression analyses using restricted cubic splines for data from studies with LSD doses of up to 200 µg base. Most scales revealed a sigmoid-like increase of effects, with a plateauing at around 100 µg. The most strongly modulated factors referred to changes in perception and illusory imagination, followed by positively experienced ego-dissolution, while only small effects were found for Anxiety and Dread of Ego Dissolution. The considerable variability observed in most factors and scales points to the role of non-pharmacological factors in shaping subjective experiences. The established dose-response relationships may be used as general references for future experimental and clinical research on LSD to compare observed with expected subjective effects and to elucidate phenomenological differences between psychedelics.

No party, no drugs? Use of stimulants, dissociative drugs, and GHB/GBL during the early COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is presumably having an impact on the consumption of psychoactive substances. Social distancing and lockdown measures may particularly affect the use of "party drugs" (e.g., stimulants, dissociatives, and GHB/GBL) through the absence of typical use settings. We aimed to analyse the use patterns of those substances and underlying motivations before and during the pandemic. METHODS: A subsample of 1,231 users of stimulants (amphetamine, methamphetamine, MDMA/ecstasy, cocaine), dissociative drugs (ketamine, dextromethorphan, PCP), and GHB/GBL was assessed from 30th April to 4th August 2020 as part of the Corona Drug Survey, a cross-sectional international online survey in five languages that included a total of 5,049 participants. The reported use of distinct substances and the underlying motivations were ascertained before (retrospectively) and during the pandemic. Furthermore, associations between drug use as a coping mechanism, pandemic-related stressors, and substance use were examined. RESULTS: Regarding the reported frequency of use during the pandemic, 48.0-64.8% of the sample ceased or decreased, 11.9-25.5% maintained, and 23.6-29.1% increased their consumption. MDMA/ecstasy showed the strongest decrease and GHB/GBL and dissociatives the highest increase. Participants reported that price, quality, and supply were mostly unaffected by the pandemic. The most common motivations before and during the pandemic were mood-related factors, such as a desire to feel exhilarated, euphoric, high, or buzzed. The relevance of social purposes and mood-related motivators declined during the pandemic, whereas dealing with boredom increased. Overall, 16.4-35.6% perceived drug use as helpful for dealing with pandemic-related stressors, which were associated with an increased consumption frequency. CONCLUSION: The early stage of the COVID-19 pandemic was associated with major changes in the use of "party drugs". Those who increased their level of drug use and perceived it as a coping strategy in particular might be targeted with adaptive preventive and therapeutic measures.

Cannabis use during the early COVID-19 pandemic: Use patterns, predictors, and subjective experiences.

Background: Even in the early stages, global crises such as the COVID-19 pandemic lead to serious dislocations of social life, secondary adjustment reactions to external restrictions and individual concerns. Coping mechanisms may also include dysfunctional strategies like an increase of drug use. Considering the wide-spread use of cannabis, the aim of this study was to elucidate the interplay of social restrictions, psychopathology, concerns related to the pandemic in addition to the users' experiences, motivations and consumption quantities during the early COVID-19 pandemic. It was presumed that cannabis intake would increase during the early phase of the crisis and that consumption quantities would be related to corona-related restrictions, concerns as well as subjective substance effects and psychopathology. Materials and methods: As part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages, consumption quantities and patterns of cannabis use in the early phase of the pandemic from April to August 2020 were examined. Participants retrospectively rated restrictions and concerns related to the pandemic, motives of cannabis use prior to and during 1 month the pandemic, and subjective consumption effects. Results: Cannabis use behavior showed no significant differences when consumption quantities prior and during 1 month after the COVID-19 outbreak were compared. Higher quantities of cannabis intake prior and during 1 month of the pandemic as well as more corona-related concern were associated with an increased perception of positive effects of cannabis during the pandemic. Predictors of its use during 1 month of pandemic were higher pre-pandemic consumption quantity, older age, quarantinization, a lesser degree of being affected by negative effects of the pandemic and a stronger subjective experience of corona-related positive effects of cannabis. Comparisons of the motives for cannabis intake in the pre-pandemic versus the pandemic period showed that all rationales for consumption were reported less frequently, except boredom. Conclusion: Frequencies of cannabis intake remained relatively stable in the early pandemic phase. Risk factors for increased use seem related to habitual consumption patterns that become more prominent under quarantinization. The use of cannabis as a dysfunctional coping strategy might not be amenable via self-report and should therefore receive special attention in clinical contexts.

Anxiety-related Symptoms following the Sporadic Use of Ecstasy - A Case Study.

3,4-methylenedioxymethamphetamine (MDMA/"ecstasy") is widespread in the electronic club scene, but MDMA has also been suggested for the treatment of anxiety spectrum disorders like posttraumatic stress disorder (PTSD) and social anxiety in autistic adults. Here, we report a case of a high functioning 24-old student with a sporadic recreational use of ecstasy, and a history of a single episode of obsessive-compulsive disorder (OCD). A few days after using ecstasy during a period of stressful life events, he developed a complex depersonalization/derealization syndrome (DDS) including intermittent distortions of time and very short intermittent episodes of misidentification of persons. Furthermore, obsessive thoughts reappeared and he suffered a panic attack for the first time in his life. Under combined pharmacological treatment and psychotherapy, symptoms gradually subsided until full remission after 14 months. Some months after discontinuation of escitalopram, however, panic attacks recurred, evolving into a regular pattern. Even if MDMA is a promising tool for the treatment of some anxiety spectrum disorders in the framework of substance-assisted psychotherapy, the use of ecstasy might be also harmful for some patients with a history of anxiety or dissociative symptoms, when used recreationally or as a self-medication outside of a controlled clinical setting.

Psychedelic Experiences During the Early COVID-19 Pandemic: Findings From an International Online Survey.

Introduction: The current corona virus disease (COVID-19) pandemic has caused a serious global health crisis that has affected large parts of the public and private life worldwide, including the use of psychoactive substances. In this study, we investigated the effect of the COVID-19 pandemic on the use of serotonergic psychedelics, i.e., the settings in which people use psychedelics, the motives of usage, and the subjective quality of psychedelic experiences. Methods: The study was part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages (English, German, Spanish, Italian, and Korean) carried out during the early phase of the pandemic from April to August 2020. Participants were asked to retrospectively rate settings and motives of psychedelic substance use before the pandemic and in the last 4 weeks during the pandemic, as well as changes in psychedelic experiences. Results: Of n = 1,375 participants that reported the use psychedelics in 2019 or 2020, n = 642 (46.6%) also took psychedelics during the pandemic. During the pandemic, participants used psychedelics significantly less often in settings that were outside their home. Top motives to use psychedelics were comparable before and during the pandemic, but participants consumed less out of curiosity, to celebrate, or because friends took it, and more out of boredom. An increase in positively connoted, often pro-social experiences was observed. Two thirds of participants who used psychedelics during the pandemic claimed that psychedelics had helped them to deal better with the corona pandemic at least slightly. Discussion: Changes in setting and motives were mostly in line with restrictions caused by control measures to contain the spread of the virus. The unexpected increase in positively connoted experiences possibly reflects a favorable interaction of environmental macro- and individual micro-contexts during the pandemic (e.g., by reducing the use in more uncontrolled recreational settings or by encouraging a strong self-selection of substance users due to the expectation of "bad trips"). Increased pro-social feelings under psychedelics might reflect a desire for social interactions in times of social distancing and pandemic-related stress and anxiety.

Predictors of Alcohol Consumption Among Younger Adults During the First Phase of the COVID-19 Pandemic.

Background: The COVID-19 pandemic may lead to negative mental health effects but the effect on alcohol consumption among younger adults is unclear. We assess predictors of change in alcohol consumption during the first phase of the COVID-19 pandemic among younger adults. Methods: This cross-sectional internet-based survey was part of an overarching project, the Corona Drug Survey, which was conducted from April 30 to August 4, 2020. Participants of any sex and ≥18 years old were included. The primary outcome measure was change in alcohol consumption during the early COVID-19 pandemic. We implemented an ordinal logistic regression to assess the effect (odds ratio [OR] and 95% confidence interval [CI]) of the following predictors: quarantine restrictions on leaving the residence, number of individuals in the household, problematic alcohol consumption before the pandemic (CAGE [cutting down, annoyance by criticism, guilty feeling, and eye-opener] score), personal concern regarding the pandemic, age, and sex. Results: 3,321 participants with a mean age of 32 (SD: 13) years were included in this study. 70.4% of participants reported less or unchanged alcohol consumption in the recent 4 weeks of the pandemic compared to before the pandemic. A higher number of individuals in the household was associated with a reduced alcohol consumption (OR = 0.869; 95% CI = 0.815-0.927). No quarantine restrictions on leaving the residence (OR = 1.593; 95% CI = 1.397-1.817), a higher age (1.006; 1.001-1.011), and female sex (compared to males: 1.206; 1.062-1.371) were associated with an increase in alcohol consumption. The CAGE score before the pandemic (OR = 0.983; 95% CI = 0.931-1.037) and the pandemic concern (0.927; 0.857-1.003) were not associated with a significant change in alcohol consumption. Celebrations were no longer frequent drinking occasions during the pandemic compared to before the pandemic. The majority of participants (60.9%) did not use alcohol drinking as a coping mechanism to mitigate negative effects of the pandemic. Interpretation: In this cohort of younger adults with fewer celebratory drinking occasions, restrictions on leaving the residence and the number of persons in the household were the strongest predictors of reduced alcohol consumption during the early phase of the pandemic.

Neuropsychological Functioning in Users of Serotonergic Psychedelics - A Systematic Review and Meta-Analysis.

Background: Serotonergic psychedelics (SPs) like LSD, psilocybin, DMT, and mescaline are a heterogeneous group of substances that share agonism at 5-HT2a receptors. Besides the ability of these substances to facilitate profoundly altered states of consciousness, persisting psychological effects have been reported after single administrations, which outlast the acute psychedelic effects. In this review and meta-analysis, we investigated if repeated SP use associates with a characteristic neuropsychological profile indicating persisting effects on neuropsychological function. Methods: We conducted a systematic review of studies investigating the neuropsychological performance in SP users, searching studies in Medline, Web of Science, embase, ClinicalTrials.gov, and EudraCT. Studies were included if they reported at least one neuropsychological measurement in users of SPs. Studies comparing SP users and non-users that reported mean scores and standard deviations were included in an exploratory meta-analysis. Results: 13 studies (N = 539) published between 1969 and 2020 were included in this systematic review. Overall, we found that only three SPs were specifically investigated: ayahuasca (6 studies, n = 343), LSD (5 studies, n = 135), and peyote (1 study, n = 61). However, heterogeneity of the methodological quality was high across studies, with matching problems representing the most important limitation. Across all SPs, no uniform pattern of neuropsychological impairment was identified. Rather, the individual SPs seemed to be associated with distinct neuropsychological profiles. For instance, one study (n = 42) found LSD users to perform worse in trials A and B of the Trail-Making task, whereas meta-analytic assessment (5 studies, n = 352) of eleven individual neuropsychological measures indicated a better performance of ayahuasca users in the Stroop incongruent task (p = 0.03) and no differences in the others (all p > 0.05). Conclusion: The majority of the included studies were not completely successful in controlling for confounders such as differences in non-psychedelic substance use between SP-users and non-users. Our analysis suggests that LSD, ayahuasca and peyote may have different neuropsychological consequences associated with their use. While LSD users showed reduced executive functioning and peyote users showed no differences across domains, there is some evidence that ayahuasca use is associated with increased executive functioning.

Do ß-Blockers Cause Depression?: Systematic Review and Meta-Analysis of Psychiatric Adverse Events During ß-Blocker Therapy.

[Figure: see text].

Connected to the spirit of the frog: An Internet-based survey on Kambô, the secretion of the Amazonian Giant Maki Frog (Phyllomedusa bicolor): Motivations for use, settings and subjective experiences.

BACKGROUND/AIM: Kambô is a name for the secretion of the Giant Maki Frog (Phyllomedusa bicolor), which has been used by indigenous cultures from the Amazonas basin and has recently become popular in alternative healing circles in Western countries, with a certain overlap with psychedelic self-exploration. METHODS: We carried out an online-based survey in English (54.92%) and German investigating motivations for using Kambô, settings in which rituals take place, and subjective experiences during and after the application. RESULTS: Participants (n = 386, mean age: 38.08 years, (standard deviation = 9.95)) were well-educated individuals with an increased lifetime prevalence of the use of ayahuasca (67.88%). A plethora of motivations for using Kambô was reported, including general healing, detoxification and spiritual growth. Acute effects included severe physical reactions and mild psychoactive effects, most surprisingly, the feeling of being connected to the frog's spirit (41.97%), whereas predominantly positive persisting psychological effects were reported. Few participants reported long-lasting physical (2.85%) or mental (1.81%) health problems which they attributed to Kambô. Of the participants, 87.31% reported an increase in personal well-being or life satisfaction, and 64.26% considered Kambô to have been at least of 'very much' spiritual significance for their lives. CONCLUSIONS: The majority of users claimed beneficial effects including more health-orientated behaviors, whereas only very few participants complained about new health problems which they ascribed to Kambô. In retrospect, Kambô was given a high personal and spiritual significance by many participants. Additional research is needed to determine in how far reported effects are modulated by setting and subjective expectations.

[Housing Situation Among People with Substance Use Disorder in a Psychiatric Centre in Berlin, Germany - A Cross-Sectional Patient Survey]. / Wohnsituation von Menschen mit Substanzgebrauchsstörungen im akut-psychiatrischen Behandlungssetting in Berlin ­ eine querschnittliche Patientenbefragung.

OBJECTIVE: To investigate the housing situation, service use and substance use among patients with substance use disorders seeking psychiatric treatment. METHODS: Structured interview among 540 psychiatric inpatients including day clinics in a psychiatric centre in Berlin, Germany. RESULTS: Patients under instable housing conditions were significantly more often diagnosed with a comorbid psychotic disorder and were significantly younger when first psychiatric or substance use treatment occurred, on average before onset of homelessness. CONCLUSION: Homelessness among people with substance use disorder seeking psychiatric treatment is associated with disadvantageous treatment factors such as early age of psychiatric treatment and comorbid psychotic disorders. Therefore, addressing social difficulties especially after inpatient treatment and close cooperation between different care providers should be of high importance among these groups.

Acute and subacute psychoactive effects of Kambô, the secretion of the Amazonian Giant Maki Frog (Phyllomedusa bicolor): retrospective reports.

Kambô, the secretion of the Amazonian Giant Leaf Frog (Phyllomedusa bicolor) contains a plethora of bioactive peptides and was originally used by indigenous communities from the Amazon basin as medicine for improving hunting capacities. In the last 20 years, Kambô has spread to Western urban healing circles. To date it is still controversial whether the acute effects of Kambô include alterations of consciousness similar to known psychoactive substance like serotonergic psychedelics. Here we retrospectively assessed psychological effects of Kambô in a sample of anonymous users (n = 22, mean age: 39 years, ± 8.5; 45.5% female), administering standardized questionnaires for the assessment of altered states of consciousness (ASC), including the Altered States of Consciousness Rating Scale, the Phenomenology of Consciousness Inventory (PCI), the Mystical Experience Questionnaire (MEQ), the Challenging Experience Questionnaire (CEQ) for acute effects and the Persisting Effects Questionnaire (PEQ) and a scale assessing connectedness for subacute effects. The intensity of retrospectively reported acute psychological effects remained on a mild to moderate level, with no psychedelic-type distortions of perception or thinking. Conversely, persisting effects were predominantly described as positive and pleasant, revealing high scores on measures of personal and spiritual significance.

Peripheral oxytocin is inversely correlated with cognitive, but not emotional empathy in schizophrenia.

Endogenous oxytocin has been associated with different aspects of social cognition in healthy subjects and patients with schizophrenia. In this pilot study, we investigated the relationship between plasma oxytocin and oxytocin level changes induced by empathy-eliciting, attachment-related movie scenes with correlates of cognitive and emotional empathy in patients and healthy controls. The Multifaceted Empathy Test (MET) and the Interpersonal Reactivity Index (IRI) were administered to patients with schizophrenia (N = 35, 12 females) and healthy controls (N = 35, 12 females) to estimate dimensions of cognitive and emotional empathy. Peripheral basal oxytocin concentrations and oxytocin responses to movie-based emotional stimuli were assessed using radioimmunoassay with sample extraction. In patients, induced oxytocin level changes were inversely correlated with MET cognitive empathy regarding negative emotional states. Controlling for non-social cognition and age revealed a significant negative association between basal oxytocin levels and MET cognitive empathy for positive emotions. In healthy subjects, oxytocin reactivity was inversely correlated with the IRI subscale "fantasy". Oxytocin was not related to any measure of emotional empathy. A hyper-reactive oxytocin system might be linked to impaired cognitive empathy as a part of a dysfunctional regulative circuit of attachment-related emotions and interpersonal stressors or threats by attribution of meaning. Healthy adults with a disposition to identify with fictional characters showed lower oxytocin reactivity, possibly indicating familiarity with movie-based stimuli. The oxytocinergic system may be involved in maladaptive coping mechanisms in the framework of impaired mentalizing and associated dysfunctional responses to interpersonal challenges in schizophrenia.

Housing situation and healthcare for patients in a psychiatric centre in Berlin, Germany: a cross-sectional patient survey.

OBJECTIVE: To determine the housing situation among people seeking psychiatric treatment in relation to morbidity and service utilisation. DESIGN: Cross-sectional patient survey. SETTING: Psychiatric centre with a defined catchment area in Berlin, Germany, March-September 2016. PARTICIPANTS: 540 psychiatric inpatients including day clinics (43.2% of all admitted patients in the study period (n=1251)). MAIN OUTCOME MEASURES: Housing status 30 days prior the interview as well as influencing variables including service use, psychiatric morbidity and sociodemographic variables. RESULTS: In our survey, 327 participants (68.7%) currently rented or owned an own apartment; 62 (13.0%) reported to be homeless (living on the street or in shelters for homeless or refugees); 87 (18.3%) were accommodated in sociotherapeutic facilities. Participants without an own apartment were more likely to be male and younger and to have a lower level of education. Homeless participants were diagnosed with a substance use disorder significantly more often (74.2%). Psychotic disorders were the highest among homeless participants (29.0%). Concerning service use, we did neither find a lower utilisation of ambulatory services nor a higher utilisation of hospital-based care among homeless participants. CONCLUSIONS: Our findings underline the need for effective housing for people with mental illness. Despite many sociotherapeutic facilities, a concerning number of people with mental illness is living in homelessness. Especially early interventions addressing substance use might prevent future homelessness.

Endogenous oxytocin response to film scenes of attachment and loss is pronounced in schizophrenia.

Background: Oxytocin (OXT) is critically involved in the regulation of attachment and interpersonal function. In this study, emotional children's movies were used to stimulate OXT secretion in patients with schizophrenia and healthy controls (HCs). Furthermore, associations of OXT levels with measures of attachment style (Psychosis Attachment Measure), childhood adversity (Childhood Trauma Questionnaire) and symptom severity [Positive and Negative Syndrome Scale (PANSS)] were considered. Methods: In 35 patients with schizophrenia and 35 matched HCs, radioimmunoassay with sample extraction was used to determine OXT plasma levels before and after viewing of movie scenes portraying emotional bonding and loss and compared to a non-emotional condition. Results: Statistical analysis indicated lower baseline OXT levels in female patients than in all other groups. OXT reactivity during emotional movies was significantly higher in patients when compared to HCs. OXT reactivity during the control movie related to PANSS `general psychopathology'. No significant associations appeared between baseline or induced OXT levels and other PANSS subscales, attachment style or childhood adversity in patients. Conclusions: Our findings suggest differences of baseline OXT and a higher OXT reactivity toward strong emotional stimuli in patients with schizophrenia, suggesting a role of OXT as a gender- and context-dependent modulator of socio-emotional function.

Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review.

Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with life-threatening diseases, often associated with a low quality of life and a poor overall prognosis. 5-HT2A-receptor agonists (serotonergic hallucinogens, 'psychedelics') like lysergic acid diethylamide (LSD) and psilocybin were first investigated as therapeutic agents in the 1960s. Recently, after a long hiatus period of regulatory obstacles, interest in the clinical use of these substances has resumed. The current article provides a systematic review of studies investigating psychedelics in the treatment of symptoms of existential distress in life-threatening diseases across different periods of research, highlighting how underlying concepts have developed over time. A systematic search for clinical trials from 1960 to 2017 revealed 11 eligible clinical trials involving a total number of N=445 participants, of which 7 trials investigated the use of lysergic acid diethylamide (LSD) (N=323), 3 trials investigated the use of psilocybin (N=92), and one trial investigated the use of dipropyltryptamine (DPT) (N=30). The 4 more recent randomized controlled trials (RCTs) (N=104) showed a significantly higher methodological quality than studies carried out in the 1960s and 1970s. Evidence supports that patients with life threatening diseases associated with symptoms of depression and anxiety benefit from the anxiolytic and antidepressant properties of serotonergic hallucinogens. Some studies anecdotally reported improvements in patients´ quality of life and reduced fear of death. Moreover, low rates of side effects were reported in studies that adhered to safety guidelines. Further studies are needed to determine how these results can be transferred into clinical practice.