Acute Effects of Hallucinogens on Functional Connectivity: Psilocybin and Salvinorin-A.

The extent of changes in functional connectivity (FC) within functional networks as a common feature across hallucinogenic drug classes is under-explored. This work utilized fMRI to assess the dissociative hallucinogens Psilocybin, a classical serotonergic psychedelic, and Salvinorin-A, a kappa-opioid receptor (KOR) agonist, on resting-state FC in nonhuman primates. We highlight overlapping and differing influence of these substances on FC relative to the thalamus, claustrum, prefrontal cortex (PFC), default mode network (DMN), and DMN subcomponents. Analysis was conducted on a within-subject basis. Findings support the cortico-claustro-cortical network model for probing functional effects of hallucinogens regardless of serotonergic potential, with a potential key paradigm centered around the claustrum, PFC, anterior cingulate cortices (ACC), and angular gyrus relationship. Thalamo-cortical networks are implicated but appear dependent on 5-HT2AR activation. Acute desynchronization relative to the DMN for both drugs was also shown. Our findings provide a framework to understand broader mechanisms at which hallucinogens in differing classes may impact subjects regardless of the target receptor.

The cyclical revival of psychedelics in psychiatric treatment.

There is an increasing demand for effective treatments for depression, particularly for individuals grappling with treatment-resistant depression. Over recent years, a surge of interest has focused on exploring the safety and efficacy of psilocybin as a potential treatment for depression. However, preliminary findings from phase 2 studies have been inconclusive, prompting critical examination of issues such as maintaining blinding and the role of adjunctive psychotherapy. The maintenance of double-blinding and the role of adjunctive psychotherapy introduce biases that complicate the attainment of conclusive results in clinical research. Examining historical data reveals a recurrent pattern linked to the use of psychoactive substances, which starts with an excess of optimism and ends with general addictive behaviors and a heightened risk of serious public health problems. Considering these findings, a cautious and measured approach is imperative, given that the efficacy and safety of psilocybin treatment have yet to be unequivocally established. The potential for excessive optimism among researchers is a notable concern, as unwarranted enthusiasm may inadvertently facilitate the widespread adoption of this treatment without sufficient empirical support. In navigating the complexities of depression treatment, it is necessary to strike a balance between innovation and prudence to ensure evidence-based advancement of therapeutic approaches.

Do classic psychedelics increase the risk of seizures? A scoping review.

Seizures are a concerning adverse event frequently associated with the use of psychedelics, and hence, studies involving these substances tend to exclude patients with past history of epilepsy. This is especially relevant because epileptic seizures are markedly increased in the population suffering from mental disorders, and psychedelic assisted therapy is being researched as a promising treatment for several of them. To determine the extent of the current literature on the relationship between classic psychedelics and seizures, a scoping review was performed using the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). The search was conducted in PubMed, Web of Science, Google scholar, LILACS and Scielo, and both animal and human models were included. A total of 16 publications on humans, and 11 on animals, were found. The results are heterogeneous, but globally suggest that psychedelics may not increase the risk of seizures in healthy individuals or animals in the absence of other drugs. However, concomitant use of other substances or drugs, such as kambo or lithium, could increase the risk of seizures. Additionally, these conclusions are drawn from data lacking sufficient external validity, so they should be interpreted with caution. Future paths for research and a summary on possible neurobiological underpinnings that might clarify the relationship between classical psychedelics and seizures are also provided.

Is Use of Psychedelic Drugs a Risk or Protective Factor for Late-Life Cognitive Decline?

Objectives: Common age-related health conditions can lead to poor mental health outcomes and deteriorate cognition. Additionally, commonly prescribed medications for various mental/physical health conditions may cause adverse reactions, especially among older adults. Psychedelic therapy has shown positive impacts on cognition and has been successful in treating various mental health problems without long-lasting adversities. The current study examines the association between psychedelic drug usage and cognitive functions in middle-aged and older adults. Methods: Data were from wave 3 (2013-2014) of the Midlife in the United States (MIDUS) study. We used multiple linear regression models examining associations between psychedelic usage and cognitive functions, controlling for covariates of sociodemographic and health factors. Results: We included 2,503 individuals (Mage = 64 ± 11). After controlling for covariates, the finding revealed that psychedelic usage was independently associated with more favorable changes in executive function (ß = .102, SE = 0.047, p = .031) and less depressive symptoms (ß = -.090, SE = 0.021, p < .001). The same effect was not found for episodic memory (ß = .039, SE = 0.066, p = .553). Discussion: Addressing the mental health implications of physical health conditions in older adults are vital for preventing neurocognitive deterioration, prolonging independence, and improving the quality of life. More longitudinal research is essential utilizing psychedelics as an alternative therapy examining late-life cognitive benefits.

XOB: A novel phenylalkylamine antagonist of 5-HT2A receptors and voltage-gated sodium channels.

Bipolar disorder impacts millions of patients in the United States but the mechanistic understanding of its pathophysiology and therapeutics is incomplete. Atypical antipsychotic serotonin2A (5-HT2A) receptor antagonists, such as quetiapine and olanzapine, and mood-stabilizing voltage-gated sodium channel (VGSC) blockers, such as lamotrigine, carbamazepine, and valproate, show therapeutic synergy and are often prescribed in combination for the treatment of bipolar disorder. Combination therapy is a complex task for clinicians and patients, often resulting in unexpected difficulties with dosing, drug tolerances, and decreased patient compliance. Thus, an unmet need for bipolar disorder treatment is to develop a therapeutic agent that targets both 5-HT2A receptors and VGSCs. Towards this goal, we developed a novel small molecule that simultaneously antagonizes 5-HT2A receptors and blocks sodium current. The new compound, N-(4-bromo-2,5-dimethoxyphenethyl)-6-(4-phenylbutoxy)hexan-1-amine (XOB) antagonizes 5-HT-stimulated, Gq-mediated, calcium flux at 5-HT2A receptors at low micromolar concentrations while displaying negligible affinity and activity at 5-HT1A, 5-HT2B, and 5-HT2C receptors. At similar concentrations, XOB administration inhibits sodium current in heterologous cells and results in reduced action potential (AP) firing and VGSC-related AP properties in mouse prefrontal cortex layer V pyramidal neurons. Thus, XOB represents a new, proof-of-principle tool that can be used for future preclinical investigations and therapeutic development. This polypharmacology approach of developing a single molecule to act upon two targets, which are currently independently targeted by combination therapies, may lead to safer alternatives for the treatment of psychiatric disorders that are increasingly being found to benefit from the simultaneous targeting of multiple receptors. Significance Statement We synthesized a novel small molecule (XOB) that simultaneously antagonizes two key therapeutic targets of bipolar disorder, 5-HT2A receptors and voltage-gated sodium channels (VGSCs), in heterologous cells, and inhibits the intrinsic excitability of mouse prefrontal cortex layer V pyramidal neurons in brain slices. XOB represents a valuable new proof-of-principle tool for future preclinical investigations and provides a novel molecular approach to the pharmacological treatment of complex neuropsychiatric disease, which often requires a combination of therapeutics for sufficient patient benefit.

The Relationship Between Changes in Mindfulness and Subsequent Changes in Well-Being Following Psychedelic Use: Prospective Cohort Study.

This study demonstrates that changes in mindfulness predict subsequent changes in well-being in a data set including individuals who recently engaged in psychedelic use.

Aggressive behaviours associated with MDMA and psychedelics: a narrative review.

OBJECTIVE: Monoamine neurotransmitters play a role in aggression, especially when altered by illicit substances. However, some literature suggests that not all illicit substances may lead to aggression, notably psychedelics. This narrative review investigates the associations between serotonergic psychedelics and MDMA on aggressive behaviour. METHODS: PubMed and PsycINFO were searched for original, peer-reviewed articles evaluating the effects of serotonergic psychedelics and 3,4-methyl enedioxy methamphetamine (MDMA) on violent and aggressive behaviour using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: After removing duplicates, a total of 555 articles were screened, with 16 meeting the inclusion criteria. One additional article was obtained through reference screening bringing the total to 17 articles. Of these 17 articles, 14 studies focused on MDMA and three on serotonergic psychedelics. Findings were mixed, with some results demonstrating increased aggression following psychedelics and others suggesting protective effects. Limitations in the current literature include varied definitions of psychedelics, lack of standardised objective outcome measures and failure to control for confounding. CONCLUSION: As psychedelic research continues to expand, further assessment on the effects of serotonergic psychedelics and MDMA on aggressive behaviour is required.

Therapeutic potential of psychedelics: History, advancements, and unexplored frontiers.

Psychedelics (serotonergic hallucinogens) are psychoactive substances that can alter perception and mood, and affect cognitive functions. These substances activate 5-HT2A receptors and may exert therapeutic effects. Some of the disorders for which psychedelic-assisted therapy have been studied include depression, addiction, anxiety and post-traumatic stress disorder. Despite the increasing number of studies reporting clinical effectiveness, with fewer negative symptoms and, additionally, minimal side effects, questions remain to be explored in the field of psychedelic medicine. Although progress has been achieved, there is still little understanding of the relationship among human brain and the modulation induced by these drugs. The present article aimed to describe, review and highlight the most promising findings in the literature regarding the (putative) therapeutic effects of psychedelics.

Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review.

The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed.

Psychedelic Drug Microdosing Practices: A Qualitative Online Exploration.

"Microdosing," defined as the consumption of small, sub-hallucinogenic quantities of psychedelic drugs, has gained recent popularity. Microdosing is a relatively new concept, therefore no scientific recommendations exist on how to prepare and consume microdoses. Many consumers obtain microdosing information online. Few studies have investigated the content of this information; thus, the present study aimed to do so by collecting a large set of online microdosing information. A qualitative approach was taken to compile and characterize online microdosing information. Medical databases, video websites, online forums, drug-specific websites and forums, search engines, and social media websites were searched. A total of 174 unique resources were found, detailing the types of substances, preparation methods, doses, schedules, and safety strategies used by people who microdose. Future research is recommended to further explore how people prepare microdoses through in-person interviews and sample collection.

Trends in hallucinogen-associated emergency department visits and hospitalizations in California, USA, from 2016 to 2022.

BACKGROUND AND AIMS: Hallucinogens encompass a diverse range of compounds of increasing scientific and public interest. Risks associated with hallucinogen use are under-researched and poorly understood. We aimed to compare the trends in hallucinogen-associated health-care use with alcohol- and cannabis-associated health-care use. DESIGN, SETTING AND CASES: We conducted an ecological study with publicly available data on International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes associated with emergency department (ED) visits and hospitalizations from the California Department of Healthcare Access and Information (HCAI). HCAI includes primary and secondary ICD-10 codes reported with ED or hospital discharge from every non-federal health-care facility licensed in California, United States, from 2016 to 2022. MEASUREMENTS: ICD-10 codes were classified as hallucinogen-, cannabis- or alcohol-associated if they were from the corresponding category in the ICD-10 block 'mental and behavioral disorders due to psychoactive substance use'. FINDINGS: Observed hallucinogen-associated ED visits increased by 54% between 2016 and 2022, from 2260 visits to 3476 visits, compared with a 20% decrease in alcohol-associated ED visits and a 15% increase in cannabis-associated ED visits. The observed hallucinogen-associated hospitalizations increased by 55% during the same period, from 2556 to 3965 hospitalizations, compared with a 1% increase in alcohol-associated hospitalizations and a 1% increase in cannabis-associated hospitalizations. This rise in hallucinogenic ED visits was significantly different from the trend in cannabis-associated (P < 0.001) and alcohol-associated (P = 0.005) ED visits. The hallucinogen-associated hospitalizations trend also significantly differed when compared with cannabis- (P < 0.001) and alcohol-associated (P < 0.001) hospitalizations. CONCLUSIONS: Hallucinogen-associated emergency department visits and hospitalizations in California, USA, showed a large relative but small absolute increase between 2016 and 2022.

Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice-from a human poisoning case to the preclinical evidence.

RATIONALE: The 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT, known online as "Moxy") is a new psychedelic tryptamine first identified on Italian national territory in 2014. Its hallucinogen effects are broadly well-known; however, only few information is available regarding its pharmaco-toxicological effects. OBJECTIVES: Following the seizure of this new psychoactive substances by the Arm of Carabinieri and the occurrence of a human intoxication case, in the current study we had the aim to characterize the in vivo acute effects of systemic administration of 5-MeO-MiPT (0.01-30 mg/kg i.p.) on sensorimotor (visual, acoustic, and overall tactile) responses, thermoregulation, and stimulated motor activity (drag and accelerod test) in CD-1 male mice. We also evaluated variation on sensory gating (PPI, prepulse inhibition; 0.01-10 mg/kg i.p.) and on cardiorespiratory parameters (MouseOx and BP-2000; 30 mg/kg i.p.). Lastly, we investigated the in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) profile of 5-MeO-MiPT compared to 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) and N,N-dimethyltryptamine (DMT). RESULTS: This study demonstrates that 5-MeO-MiPT dose-dependently inhibits sensorimotor and PPI responses and, at high doses, induces impairment of the stimulated motor activity and cardiorespiratory changes in mice. In silico prediction shows that the 5-MeO-MiPT toxicokinetic profile shares similarities with 5-MeO-DIPT and DMT and highlights a cytochrome risk associated with this compound. CONCLUSIONS: Consumption of 5-MeO-MiPT can affect the ability to perform activities and pose a risk to human health status, as the correspondence between the effects induced in mice and the symptoms occurred in the intoxication case suggests. However, our findings suggest that 5-MeO-MiPT should not be excluded from research in the psychiatric therapy field.

Development of the Protective Strategies for Psychedelics Scale: A novel inventory to assess safety strategies in the context of psychedelics.

BACKGROUND: Individuals who use psychedelics take efforts to mitigate unintended consequences. Despite the demonstrated utility of analogous protective behavioral strategies (PBS) assessments for other substances, no standardized scale exists to capture these protective strategies for psychedelic use. OBJECTIVE: The present study addresses a notable gap concerning the assessment of psychedelic use, specifically by developing a scale measuring the protective strategies employed around use, called the Protective Strategies for Psychedelics Scale (PSPS). METHODS: A sample (Mage = 36.85 years old, standard deviation = 10.3; male = 61.9%; White = 85.2%) of 434 adults with lifetime use of psychedelics reported on initial qualitatively developed items for the PSPS, PBS scales for cannabis and alcohol, and use of alcohol, cannabis, and psychedelics. RESULTS: Iterative principal components analyses began with 37 items and yielded a 32-item two-factor solution demonstrating excellent internal reliability (Cronbach's α = .95) and accounted for 51.3% of the variance. Nineteen items loaded on PSPS factor 1, which focused on long-term preparation, emphasizing strategies focused on mood/intentions, preparing the substance, environment, and scheduling episode of use; 13 items loaded on factor 2, which focused on short-term preparation, highlighting strategies surrounding social context, health, and other substances. The PSPS demonstrated convergent validity with validated PBS scales for cannabis and alcohol (r = 0.71-0.79, p < 0.001), and was moderately associated with lifetime psychedelic use (r = 0.28, p < 0.001). CONCLUSION: The PSPS demonstrates promising psychometric properties, and future work validating the scale for diverse samples across research and clinical settings is warranted.

Hypothetical biosynthetic pathways of pharmaceutically potential hallucinogenic metabolites in Myristicaceae, mechanistic convergence and co-evolutionary trends in plants and humans.

The family Myristicaceae harbour mind-altering phenylpropanoids like myristicin, elemicin, safrole, tryptamine derivatives such as N,N-dimethyltryptamine (DMT) and 5-methoxy N,N-dimethyltryptamine (5-MeO-DMT) and ß-carbolines such as 1-methyl-6-methoxy-dihydro-ß-carboline and 2-methyl-6-methoxy-1,2,3,4-tetrahydro-ß-carboline. This study aimed to systematically review and propose the hypothetical biosynthetic pathways of hallucinogenic metabolites of Myristicaceae which have the potential to be used pharmaceutically. Relevant publications were retrieved from online databases, including Google Scholar, PubMed Central, Science Direct and the distribution of the hallucinogens among the family was compiled. The review revealed that the biosynthesis of serotonin in plants was catalysed by tryptamine 5-hydroxylase (T5H) and tryptophan 5-hydroxylase (TPH), whereas in invertebrates and vertebrates only by tryptophan 5-hydroxylase (TPH). Indolethylamine-N-methyltransferase catalyses the biosynthesis of DMT in plants and the brains of humans and other mammals. Caffeic acid 3-O-methyltransferase catalyses the biosynthesis of both phenylpropanoids and tryptamines in plants. All the hallucinogenic markers exhibited neuropsychiatric effects in humans as mechanistic convergence. The review noted that DMT, 5-MeO-DMT, and ß-carbolines were natural protectants against both plant stress and neurodegenerative human ailments. The protein sequence data of tryptophan 5-hydroxylase and tryptamine 5-hydroxylase retrieved from NCBI showed a co-evolutionary relationship in between animals and plants on the phylogenetic framework of a Maximum Parsimony tree. The review also demonstrates that the biosynthesis of serotonin, DMT, 5-MeO-DMT, 5-hydroxy dimethyltryptamine, and ß-carbolines in plants, as well as endogenous secretion of these compounds in the brain and blood of humans and rodents, reflects co-evolutionary mutualism in plants and humans.

Drug-drug interactions involving classic psychedelics: A systematic review.

Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug-drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects.

Adaptation and latent structure of the Brazilian version of the Ego Dissolution Inventory (EDI-BR): an exploratory study

Abstract Objective Existing scales that seek to measure alterations in self-experience were developed based on studies conducted in developed countries. Therefore, the aim of this study was to evaluate the psychometric properties of the Ego Dissolution Inventory (EDI) after translating and adapting it for the Brazilian context. Methods The measure was translated by two translators fluent in both English and Portuguese, followed by back-translation into English to ensure there was no loss of meaning. The scale was used in an online survey exploring substance use. A total of 528 participants answered the full scale. We calculated the Kaiser-Meyer-Olkin (KMO) measure to evaluate sampling adequacy, then ran exploratory factor analysis (EFAs) to investigate the factor structure of the EDI. Results The scale showed acceptable psychometric properties, with excellent internal consistency and sampling adequacy for factor analysis. Kaiser-Guttman's criteria and Hull's method indicated a three-factor solution, while parallel analysis suggested a two-factor solution. All items showed salient loadings, with two items exhibiting cross-loading. Positive but weak correlations were found between EDI factors 1 and 2 and nature relatedness. Conclusions The validated scale showed solid psychometric properties, with potential differences in factor structure in relation to the English version. Considering validation is an ongoing process, it is recommended that studies be conducted comparing ego dissolution scores across distinct substances and different regions of the country.

Psychedelic Drugs or Hallucinogens: Exploring Their Medicinal Potential.

Serotonergic hallucinogens also referred to as psychedelics, are psychoactive substances that profoundly alter perception, mood, and cognitive processes. These substances, historically intertwined with religious and cultural rituals, offer profound effects that extend beyond mere hallucinations to profoundly altered states of consciousness. Notable compounds like Lysergic acid diethylamide (LSD) and psilocybin, potent in their action on serotonin receptors, play pivotal roles in influencing brain functions. Despite societal misconceptions that have overshadowed their potential, contemporary research increasingly recognizes their therapeutic value. These substances have shown promise in treating neuropsychiatric disorders such as depression, post-traumatic stress disorder (PTSD), and anxiety, leveraging their influence on neuroplasticity. Furthermore, they exhibit therapeutic potential across various conditions, challenging conventional treatment methodologies. Compared to substances like alcohol, traditional psychedelics like LSD and psilocybin emerge as relatively safer substances. The modern revival of scientific interest in psychedelics necessitates a renewed perspective, viewing them not just as recreational entities but as potent therapeutic tools. Harnessing their actual value mandates rigorous scientific investigations and a receptive societal discourse. A re-evaluation of their classification following international criteria is necessary in light of this increasing understanding. Hallucinogens or psychedelic drugs, if used correctly, can potentially be potential treatments for mental illness, signalling a paradigm shift from traditional techniques. To dispel myths and use their therapeutic advantages, embracing this potential necessitates thorough scientific investigation together with an open societal discourse.

Efficacy and Safety of Psychedelics in Treating Anxiety Disorders.

Background: Anxiety disorders are commonly diagnosed and cause substantial functional impairment. A mixture of pharmacologic and psychosocial treatments currently exists, but these treatments are not always tolerable and effective. For patients with anxiety resistant to standard therapy, psychedelics may be a promising alternative. This review assesses the therapeutic benefits and safety of psychedelics in treating anxiety disorders. Methods: We searched PubMed, Embase, PsycInfo, and CINAHL for clinical trials investigating psychedelics in patients with clinician-diagnosed generalized anxiety disorder, social anxiety disorder, specific phobia, separation anxiety disorder, selective mutism, panic disorder, agoraphobia, and anxiety attributable to another medical condition. We analyzed data from 9 independent psychedelic-assisted trials testing ayahuasca (1 study), ketamine (4 studies), lysergic acid diethylamide (LSD) (2 studies), 3,4-methylenedioxymethamphetamine (MDMA) (1 study), and psilocybin (1 study). Efficacy was assessed by measuring the change in outcome measures and the quality of life from baseline. Results: The reviewed studies demonstrated encouraging efficacy in reducing anxiety symptoms, increasing self-perception, and increasing social function in patients with generalized anxiety disorder, social anxiety disorder, or anxiety attributable to another medical condition while establishing feasibility and evidence of safety. For many patients, the therapeutic effects of the psychedelic treatment lasted weeks, and no severe adverse events were reported. Conclusion: Based on the evidence of symptom reduction and safety, the current literature (2011 to 2021) shows that psychedelics could be considered for treating clinician-diagnosed anxiety disorders. Psychedelics may provide an alternative therapeutic option for patients resistant to current standard treatments.