Lifetime classic psychedelic use and headaches: A cross-sectional study.

Mental health problems are endemic across the globe, and suicide, a strong corollary of poor mental health, is a leading cause of death. Classic psychedelic use may occasion lasting improvements in mental health, but the effects of classic psychedelic use on suicidality are unknown. We evaluated the relationships of classic psychedelic use with psychological distress and suicidality among over 190,000 USA adult respondents pooled from the last five available years of the National Survey on Drug Use and Health (2008-2012) while controlling for a range of covariates. Lifetime classic psychedelic use was associated with a significantly reduced odds of past month psychological distress (weighted odds ratio (OR)=0.81 (0.72-0.91)), past year suicidal thinking (weighted OR=0.86 (0.78-0.94)), past year suicidal planning (weighted OR=0.71 (0.54-0.94)), and past year suicide attempt (weighted OR=0.64 (0.46-0.89)), whereas lifetime illicit use of other drugs was largely associated with an increased likelihood of these outcomes. These findings indicate that classic psychedelics may hold promise in the prevention of suicide, supporting the view that classic psychedelics' most highly restricted legal status should be reconsidered to facilitate scientific study, and suggesting that more extensive clinical research with classic psychedelics is warranted.

Background and aimsAlthough large-scale population studies have linked the use of classic psychedelics (lysergic acid diethylamide, psilocybin, or mescaline) to reduced odds of physical health problems, mental health problems, and criminal behavior, the roughly 35 million adults in the United States who have used classic psychedelics are nonetheless stigmatized in the American job market. Various federal organizations in the United States automatically reject applicants on the sole basis of prior psychedelic use, thereby practicing an open form of legal discrimination against these applicants. The present study investigates whether this discrimination can be justified based on associations between lifetime classic psychedelic use and motivationally-based workplace absenteeism.MethodsUsing pooled cross-sectional data from the National Survey on Drug Use and Health (2013–2019) on 193,320 employed adults in the United States, this study tests whether lifetime classic psychedelic use predicts the number of workdays employees skipped in the last month (i.e., motivationally-based workplace absenteeism).ResultsAfter adjusting for sociodemographics, physical health indicators, and other substance use, no significant association between lifetime classic psychedelic use and motivationally-based workplace absenteeism is found.ConclusionThis study builds on classic psychedelic research that is just beginning to take work-specific outcomes into account and offers empirical justification for the elimination of arbitrary drug-based recruitment policies in the workplace.

Different psychoactive substances are widely used in today's society. So far limited data are available on the use of psychedelics in the general population. The main aim of this study is to estimate the numbers of users of substances with psychedelic properties (classical psychedelics, cannabis, ecstasy, and ketamine) in the Czech Republic. Data from two samples enrolled in representative cross-sectional questionnaire surveys in the Czech adult population in 2016 (n = 2,785) and 2018 (n = 1,665) were analysed. Prevalence rates were extrapolated to estimate numbers of current, i.e., last-year, users of psychedelics, and their socio-demographic profiles were compared with non-users and users of cannabis. An estimated 5-6% of the Czech adult population (350-430 thousand people) used classical psychedelics (LSD, psilocybin mushrooms, ayahuasca) in their lifetime, increasing up to 28-30% when cannabis is included (1.9-2.1 million users). Current use of classical psychedelics reached 0.7-1.9% (50-130 thousand people), and 9-11% (590-750 thousand users) when cannabis was included. Users of psychedelics were more often males, of younger age and single. No significant socio-demographic differences were found between users of classical psychedelics and recreational cannabis users, however, differences were significant when compared to non-users and users of other illicit drugs. Findings should further serve to inform drug policy and social and healthcare systems in respect to the use of psychedelics.

Objectives: Absenteeism from work due to illness, and related costs, has increased steadily during the past decades. In recent years, there has been a reemergence of research on the therapeutic effects of classic psychedelics showing associations with both physical and mental health. However, the association between classic psychedelics and sick leave remains unknown. The aim of this study is to investigate the association between lifetime classic psychedelic use and sick leave in the past 30 days among adults in the United States (N = 407,717), using data from the National Survey on Drug Use and Health (2005–2019), weighted to be representative of the US adult population. Methods: The primary analysis was conducted using multiple linear regression, controlling for sociodemographic characteristics, risky behavior, and use of other substances. Results: There was a significant and negative association between lifetime classic psychedelic use and sick leave in the past 30 days (B = −0.09, p < 0.01) when adjusting for all control variables. Conclusion: These findings suggest that classic psychedelics could potentially lead to reduced sick leave and associated costs in the general population, but more research is needed to investigate potential causal pathways of classic psychedelics on sick leave and evaluate possible mechanisms.

Cocaine Use Disorder (CUD) is a significant public health problem associated with elevated morbidity and mortality within the United States. Current behavioral treatments have limited efficacy and there are currently no FDA approved pharmacological treatments for CUD. Classic psychedelics might be associated with lowered odds of substance misuse and may effectively treat various forms of addiction. Thus, the goal of this study is to assess protective associations that lifetime use of classic psychedelics may share with CUD within a nationally representative sample of the U.S. We used data from The National Survey on Drug Use and Health (NSDUH) (2015–2019) and conducted survey-weighted multivariable logistic regression to test whether each of four classic psychedelics (peyote, mescaline, psilocybin, LSD) conferred lowered odds of CUD and its related 11 sub-criteria. Participants were 214,505 adults in the NSDUH (2015–2019) aged 18 and older. Peyote conferred lowered odds of CUD, reducing the odds of CUD by over 50% (aOR: 0.47). All other substances (including other classic psychedelics) either shared no association to CUD or conferred increased odds of CUD. Furthermore, sensitivity analyses revealed peyote to confer sharply lowered odds of the majority (seven of 11) of CUD criteria as well (aOR range: 0.26–0.47). Peyote use is associated with lowered odds of CUD. Future inquiries into third variable factors (i.e., demographic/personality profiles of individuals who use peyote, motivational/contextual factors surrounding peyote use) that may underlie our observed associations may reveal protective factors that can inform treatment development for CUD. Additionally, future longitudinal studies can shed further light on whether there is a temporal link between peyote use and lowered odds of CUD.

Emerging evidence suggests that classical psychedelics possess immunomodulatory and anti-inflammatory properties; however, these effects are yet to be well-established. This systematic review aims to provide a timely and comprehensive overview of the immunomodulatory effects of classical psychedelics in preclinical studies. A systematic search was conducted on six databases, including CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus, and Web of Science. Eligible studies targeting classical psychedelics for evaluation of their effects on inflammatory markers and immunomodulation have been included for analysis. Data was extracted from 40 out of 2822 eligible articles, and their risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool and Quality Assessment Tool for In Vitro Studies (QUIN). Studies examined 2,5-dimethoxy-4-iodoamphetamine (DOI; n = 18); psilocybin (4-PO-DMT; n = 9); N,N-dimethyltryptamine (DMT; n = 8); lysergic acid diethylamide (LSD; n = 6); 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; n = 3); psilocin (4-HO-DMT; n = 3); and mescaline (n = 2). In 36 studies where inflammatory cytokine levels were measured following psychedelic administration, a decrease in at least one inflammatory cytokine was observed in 29 studies. Immune cell activity was assessed in 10 studies and findings were mixed, with an equal number of studies (n = 5 out of 10) reporting either an increase or decrease in immune cell activity. Classical psychedelics were found to alleviate pre-existing inflammation but promote inflammation when administered under normal physiological conditions. This information is anticipated to inform future clinical trials, exploring classical psychedelics' potential to alleviate inflammation in various pathologies.

Psychotic symptoms are uncommon and non-specific adverse effects of classic (serotonergic) psychedelics such as lysergic acid diethylamide (LSD), psilocybin, and mescaline. They can emerge during the acute phase of psychedelic drug effects, persist into the subacute ("afterglow") period, or, in rare cases, develop into long-term psychotic illness. Across all three scenarios, the symptoms can be deeply distressing due to their rapid changes, unpredictability, and significant adverse behavioral consequences.Psychedelics have a long history of use as research models for schizophrenia because of the phenomenological overlaps between their acute effects and the core symptoms of psychosis. This "model psychosis" paradigm, however, has been widely criticized: although certain acute symptoms may appear similar, the etiology and psychodynamic background of primary psychosis only partially apply to psychedelic-related psychosis. Moreover, it remains unclear whether psychotic symptoms following the use of classic psychedelics differ meaningfully from those associated with other substances, such as dopaminergic stimulants or cannabis.A transient porosity of ego boundaries is a core feature of acute psychedelic states, ranging from heightened feelings of connectedness with oneself and others to complete ego dissolution. These experiences are often perceived as positive and may be followed by a subacute phase characterized by sustained increases in openness to new experiences. In some cases, however, ego dissolution may become fear-inducing and progress from challenging but manageable experiences to paranoid psychotic reactions that require therapeutic guidance and intervention.In this chapter, we examine phenomenological similarities and differences between psychedelic-induced psychosis and primary psychosis. Consistent with current international diagnostic classification systems, we conclude that, with increasing temporal distance from the initial psychedelic "index" experience that predated the symptoms, persisting psychedelic-induced psychotic symptoms become indistinguishable from primary psychosis. Finally, we present a psychodynamic therapeutic approach for schizophrenia-spectrum psychosis that may, to some extent, be adapted to psychotic symptoms observed across all three phases of psychedelic drug effects.

Interest in classical psychedelics as potential treatments for ADHD has grown alongside broader psychiatric psychedelic research, but ADHD-specific evidence remains limited. This systematic review examined prospective and experimental studies on whether classical psychedelics, including microdosing-like use and retreat-based exposure, are associated with changes in adult ADHD symptoms and related functioning. A PRISMA-guided systematic review was conducted using a PECO/PICO framework focused on adults (≥18 years) with diagnosed ADHD and/or elevated ADHD symptomatology who were exposed to a classical psychedelic and assessed prospectively with quantitative ADHD outcomes. Major databases were searched, with reference screening and targeted checks for recent or registered trials. Risk of bias was assessed using RoB 2 for the RCT and ROBINS-I for non-randomized studies. Because of heterogeneity and the small number of studies, findings were synthesized narratively. Five studies met the inclusion criteria. Five prospective/experimental studies were included: three naturalistic online microdosing cohorts, one randomized double-blind placebo-controlled phase 2A trial of low-dose LSD, and one pre-post ayahuasca retreat pilot. In uncontrolled naturalistic microdosing studies, participants reported short-term reductions in ADHD symptom ratings together with improvements in well-being and affect-related functioning; however, these studies were highly vulnerable to self-selection, expectancy, attrition, and non-standardized exposure. In contrast, the only randomized placebo-controlled ADHD trial found improvement in both LSD and placebo groups, with no statistically significant advantage for LSD on clinician-rated or self-reported ADHD outcomes. Objective cognitive findings were limited and inconsistent, and safety data outside the supervised trial context were sparse. Naturalistic studies provide, at most, low-certainty signals of perceived short-term improvement, but the strongest controlled evidence does not demonstrate drug-specific efficacy of repeated low-dose LSD for core ADHD symptoms. Current evidence therefore does not allow separation of pharmacological effects from expectancy, setting, self-monitoring, and broader experiential/contextual influences, and is insufficient to support psychedelics as an evidence-based treatment for ADHD.

We aim to provide an evidence-based overview of the use of psychedelics in chronic pain, specifically LSD and psilocybin. Chronic pain is a common and complex problem, with an unknown etiology. Psychedelics like lysergic acid diethylamide (LSD) and psilocybin, may play a role in the management of chronic pain. Through activation of the serotonin-2A (5-HT2A) receptor, several neurophysiological responses result in the disruption of functional connections in brain regions associated with chronic pain. Healthy reconnections can be made through neuroplastic effects, resulting in sustained pain relief. However, this process is not fully understood, and evidence of efficacy is limited and of low quality. In cancer and palliative related pain, the analgesic potential of psychedelics was established decades ago, and the current literature shows promising results on efficacy and safety in patients with cancer-related psychological distress. In other areas, patients suffering from severe headache disorders like migraine and cluster headache who have self-medicated with psychedelics report both acute and prophylactic efficacy of LSD and psilocybin. Randomized control trials are now being conducted to study the effects in cluster headache Furthermore, psychedelics have a generally favorable safety profile especially when compared to other analgesics like opioids. In addition, psychedelics do not have the addictive potential of opioids. Given the current epidemic use of opioids, and that patients are in desperate need of an alternative treatment, it is important that further research is conducted on the efficacy of psychedelics in chronic pain conditions.

Classic psychedelics show promise in the treatment of mental health conditions; however, more scalable intervention protocols are needed to maximize access to these novel therapeutics. In this proof-of-concept study, perceptions of safety, subjective effects, and beliefs about the clinical utility of lysergic acid diethylamide (LSD) were evaluated among healthy participants (N = 31) administered 50 to 100 µg LSD in a treatment paradigm conceptualized as more scalable than traditional approaches to administering classic psychedelics. Semi-structured interviews assessed participants' expectations, experience, and thoughts on the safety and efficacy of the study design. These interviews were transcribed for thematic analysis relating to perceptions of safety, subjective effects, and beliefs about the clinical utility of LSD. Most participants felt safe throughout the study, with a minority reporting concerns related to having a challenging experience that diminished over time. Participants attributed their feelings of safety to the study structure and support of their attendants, which allowed them to "let go" and immerse themselves in the experience without pre-occupation. Furthermore, participants reported transcendent, mystical-type experiences characteristic of classic psychedelics, with almost half highlighting the prominent role played by music during the acute period of drug action. Finally, participants endorsed support for the clinical utility of LSD in controlled environments, expressing the belief that LSD is safe and has the potential to help others. Findings provide preliminary support for the feasibility of this scalable interventional paradigm and set the stage for future critical research with clinical populations.

Recent controversies have arisen regarding claims of uncritical positive regard and hype surrounding psychedelic drugs and their therapeutic potential. Criticisms have included that study designs and reporting styles bias positive over negative outcomes. The present study was motivated by a desire to address this alleged bias by intentionally focusing exclusively on negative outcomes, defined as self-perceived ‘negative’ psychological responses lasting for at least 72 h after psychedelic use. A strong justification for this selective focus was that it might improve our ability to capture otherwise missed cases of negative response, enabling us to validate their existence and better examine their nature, as well as possible causes, which could inspire risk-mitigation strategies. Via advertisements posted on social media, individuals were recruited who reported experiencing negative psychological responses to psychedelics (defined as classic psychedelics plus MDMA) lasting for greater than 72 h since using. Volunteers were directed to an online questionnaire requiring quantitative and qualitative input. A key second phase of this study involved reviewing all of the submitted cases, identifying the most severe—e.g., where new psychiatric diagnoses were made or pre-existing symptoms made worse post psychedelic-use—and inviting these individuals to participate in a semi-structured interview with two members of our research team, during which participant experiences and backgrounds were examined in greater depth. Based on the content of these interviews, a brief summary of each case was compiled, and an explorative thematic analysis was used to identify salient and consistent themes and infer common causes. 32 individuals fully completed an onboarding questionnaire (56% male, 53% < age 25); 37.5% of completers had a psychiatric diagnosis that emerged after their psychedelic experience, and anxiety symptoms arose or worsened in 87%. Twenty of the seemingly severer cases were invited to be interviewed; of these, 15 accepted an in-depth interview that lasted on average 60 min. This sample was 40% male, mean age = 31 ± 7. Five of the 15 (i.e., 33%) reported receiving new psychiatric diagnoses after psychedelic-use and all fifteen reported the occurrence or worsening of psychiatric symptoms post use, with a predominance of anxiety symptoms (93%). Distilling the content of the interviews suggested the following potential causal factors: unsafe or complex environments during or surrounding the experience, unpleasant acute experiences (classic psychedelics), prior psychological vulnerabilities, high- or unknown drug quantities and young age. The current exploratory findings corroborate the reality of mental health iatrogenesis via psychedelic-use but due to design limitations and sample size, cannot be used to infer on its prevalence. Based on interview reports, we can infer a common, albeit multifaceted, causal mechanism, namely the combining of a pro-plasticity drug—that was often ‘over-dosed’—with adverse contextual conditions and/or special psychological vulnerability—either by young age or significant psychiatric history. Results should be interpreted with caution due to the small sample size and selective sample and study focus.

Recent clinical and preclinical evidence points towards empathogenic and prosocial effects elicited by psychedelic compounds, notably the serotonin 5-HT2A agonists lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), and their derivatives. These findings suggest a therapeutic potential of psychedelic compounds for some of the behavioural traits associated with autism spectrum disorder (ASD), a neurodevelopmental condition characterized by atypical social behaviour. In this review, we highlight evidence suggesting that psychedelics may potentially ameliorate some of the behavioural atypicalities of ASD, including reduced social behaviour and highly co-occurring anxiety and depression. Next, we discuss dysregulated neurobiological systems in ASD and how they may underlie or potentially limit the therapeutic effects of psychedelics. These phenomena include: 1) synaptic function, 2) serotonergic signaling, 3) prefrontal cortex activity, and 4) thalamocortical signaling. Lastly, we discuss clinical studies from the 1960s and 70s that assessed the use of psychedelics in the treatment of children with ASD. We highlight the positive behavioural outcomes of these studies, including enhanced mood and social behaviour, as well as the adverse effects of these trials, including increases in aggressive behaviour and dissociative and psychotic states. Despite preliminary evidence, further studies are needed to determine whether the benefits of psychedelic treatment in ASD outweigh the risks associated with the use of these compounds in this population, and if the 5-HT2A receptor may represent a target for social-behavioural disorders.

Objective Recent years have witnessed a resurgence in research exploring the therapeutic potential of classic psychedelics like psilocybin and LSD for treating mental disorders. However, there is a limited knowledge regarding the epidemiology of classic psychedelics consumption and the factors associated with their recreational use in Poland. Methods A representative sample of Polish citizens (N=1051 adults) completed an internet-based survey encompassing demographic inquiries, evaluations of psychedelic substance consumption including motivations and contexts, subjective assessments of psychedelics experience and evaluation of attitudes towards psychodelics and psychedelic-assisted therapy. Results Our study revealed that approximately 4% to 8% of Polish individuals, equivalent to around 2 million people, have experimented with psychedelic substances at least once in their lives. Men exhibited a higher likelihood of psychedelic use compared to women, with the largest cohort of users falling within the 25-34 age bracket and residing in urban areas. The most common motivation for reaching them was curiosity. The psychedelic experience was commonly described as a mixture of pleasant and unpleasant sensations. A significant portion of participants expressed a negative attitude towards psychedelics and psychedelic-assisted therapy, but previous experience with psychodelics was associated with more positive attitudes. Conclusions In this representative sample of Poles, we found a substantial percentage of adults who recreationally used classic psychedelics, with majority of them being young men coming from big cities. More studies are needed as well as educational programs that may foster scientific research into psychedelic therapy in Poland and the attitudes of Poles toward it.

Objective Naratriptan has been reported to reduce the frequency of cluster headache. The purpose of this study was to determine whether naratriptan is effective as a prophylactic treatment for cluster headache in Japan. Methods We retrospectively reviewed all 43 patients with cluster headache who received preventive treatment with naratriptan from April 2009 to April 2015. The International Classification of Headache Disorders, 3rd Edition (beta version) (ICHD-3 beta) was used to diagnose cluster headache. This study was conducted at 3 centers (Department of Neurology, Saitama Medical University; Saitama Neuropsychiatric Institute; Saitama Medical University International Medical Center). Patients were recruited from these specialized headache outpatient centers. Naratriptan was taken before the patient went to bed. Results The study population included 30 men (69.8%) and 13 women (30.2%). Twenty-two cases received other preventive treatments (51.2%), while 21 cases only received naratriptan (48.8%). Among the 43 cases, 37 patients (86.0%) achieved an improvement of cluster headache on naratriptan. Conclusion Naratriptan has been suggested as a preventive medicine for cluster headache because of the longer the biological half-life in comparison to other triptans. The internal use of naratriptan 2 hours before attacks appears to achieve a good response in patients with cluster headache.

Prior research has found an association between psychedelic use and reduced stigma attached to mental illness. However, whether psychedelics alleviate stigma-related distress remains unclear. Since stigma impacts different groups uniquely, any moderating effect of psychedelics on stigma-related distress is likely to vary across subpopulations. This study addresses two main questions: (1) Do psychedelics moderate the relationship between stigma and distress? and (2) does this relationship vary by gender and race/ethnicity? By exploring these questions, this research seeks to contribute to our understanding of psychedelic use and its impact on mental health across diverse populations. Data from the National Survey of Drug Use (2008-2019) were analyzed, with a weighted sample of 458,372. The main analysis used regression models in Stata 18 to examine the associations between lifetime psychedelic use (LPU) (psilocybin, lysergic acid diethylamide [LSD], N,N-dimethyltryptamine, peyote/mescaline, ayahuasca, and 3,4-Methylenedioxymethamphetamine), stigma attached to seeking mental health care, and psychological distress. This analysis examines whether the association between stigma and distress differs by gender, race/ethnicity, and psychedelic use (i.e., White men, White women, Black men, Black women, Asian men, Asian women, Hispanic men, and Hispanic women). Results indicate that men report lower perceived stigma than women, while women report higher distress. White, Black, and Hispanic women report the highest stigma levels. Regression analysis suggests that among the total population, stigma is statistically associated with higher distress, and interaction terms indicate that MDMA, psilocybin, LSD, and LPU are linked to variations in this relationship. Regression models stratified by gender and race/ethnicity suggest that while LPU, LSD, and DMT were statistically associated with differences in the relationship between stigma and distress for White men, these associations appeared weaker for other groups. Psychedelic use is associated with lower reported distress from internalized stigma, though the directionality and mechanisms underlying this association remain unclear. Further research should be conducted to investigate how psychedelics can be integrated into comprehensive health treatment programs outside of psychedelics-assisted therapy. However, it is worth noting that individuals from gender and racial/ethnic minority groups may not experience the same level of benefits, suggesting other strategies may be necessary to address the stigma experienced by different groups.