Dimethyltryptamine Research Articles

How do psychostimulants enter the human brain? Analysis of the role of the proton-organic cation antiporter

BackgroundAlthough psychostimulants apparently do cross the BBB, it is poorly understood how these hydrophilic and positively charged molecules can pass the blood-brain barrier (BBB). That may be mediated by a genetically still uncharacterized H+/OC antiporter with high activity at the BBB. MethodsWe studied the uptake of 16 psychostimulants and hallucinogens with hCMEC/D3 cells using the prototypic inhibitor imipramine (cis-inhibition), exchange transport with diphenhydramine and clonidine (trans-stimulation), proton dependency of the uptake, and we characterized the concentration-dependent uptake. ResultsCell uptake of methylenedioxyamphetamines, amphetamines and dimethyltryptamine (DMT) were strongly inhibited (to about 10% of the controls) by imipramine and diphenhydramine, whereas uptake of cathine was only weakly inhibited and mescaline not significantly.Amphetamine, methylamphetamine, para-Methoxy-N-methylamphetamine (PMMA), Methylenedioxymethamphetamine (MDMA), phentermine and DMT exhibited the highest exchange after preloading with diphenhydramine with only 5.5%, 5.2%, 7.8%, 6%, 1.9%, 7.6% remaining in the cells. Less and no exchange were seen with cathine and mescaline, respectively.Dependence on intracellular pH was most pronounced with the methylendioxyamphetamines while uptake of cathine, DOI and cocaine were only moderately affected and mescaline not at all. ConclusionExcept for mescaline, all psychostimulants studied here were substrates of the H+/OC antiporter, implicating a strong need for a better characterization of this transport protein.

Lysergic Acid Diethylamide, Psilocybin and Dimethyltryptamine in Depression Treatment: A Systematic Review.

Despite many different kinds of substances available for depression treatment, depression itself still appears to be a clinical challenge. Recently, formerly illicit substances came to scientists’ attention, including lysergic acid diethylamide (LSD), psilocybin and dimethyltryptamine (DMT). Some studies suggest that these substances might be effective in depression treatment. The aim of this study was to evaluate the efficiency of LSD, psilocybin and DMT in depression treatment in the light of current medical literature. The authors followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for this systematic review. The authors searched the PubMed and Cochrane Library databases to identify relevant publications. Finally, 10 papers were included. Most of the selected studies showed significant correlation between psilocybin and DMT use and reduction in depression symptom intensity. By analyzing qualified studies, it can be concluded that psilocybin and DMT could be useful in depression treatment, but further observations are still required.

N,N-Dimethyltryptamine attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain

Dimethyltryptamine (DMT), an endogenous ligand of sigma-1 receptors (Sig-1Rs), acts against systemic hypoxia, but whether DMT may prevent cerebral ischemic injury is unexplored. Here global forebrain ischemia was created in anesthetized rats and aggravated with the induction of spreading depolarizations (SDs) and subsequent short hypoxia before reperfusion. Drugs (DMT, the selective Sig-1R agonist PRE-084, the Sig-1R antagonist NE-100, or the serotonin receptor antagonist asenapine) were administered intravenously alone or in combination while physiological variables and local field potential from the cerebral cortex was recorded. Neuroprotection and the cellular localization of Sig-1R were evaluated with immunocytochemistry. Plasma and brain DMT content was measured by 2D-LC-HRMS/MS. The affinity of drugs for cerebral Sig-1R was evaluated with a radioligand binding assay. Both DMT and PRE-084 mitigated SDs, counteracted with NE-100. Further, DMT attenuated SD when co-administered with asenapine, compared to asenapine alone. DMT reduced the number of apoptotic and ferroptotic cells and supported astrocyte survival. The binding affinity of DMT to Sig-1R matched previously reported values. Sig-1Rs were associated with the perinuclear cytoplasm of neurons, astrocytes and microglia, and with glial processes. According to these data, DMT may be considered as adjuvant pharmacological therapy in the management of acute cerebral ischemia.

The need for publicly funded research on therapeutic use of psychedelic drugs.

The need for publicly funded research on therapeutic use of psychedelic drugs.

The Potential Role of Psychedelic Drugs in Mental Health Care of the Future.

Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide (LSD), or dimethyltryptamine (DMT), as well as psychoactive drugs that trigger phenomenologically- related experiences like 3,4-methylenedioxymethamphetamine (MDMA) and ketamine, belong to the most promising treatment approaches in contemporary psychiatry. Psychedelic-assisted psychotherapy is not only a new treatment paradigm in psychopharmacology, but it also requires a redefinition of psychotherapeutic processes and the contextualization of psychopharmacological interventions within a new treatment infrastructure. Crucial for future practice and research in the field are (1) informed patient referral and co-treatment practices, (2) screening (e. g., choosing the right patients for these therapies), (3) the dosing preparation sessions, (4) the assisted dosing sessions as well as after-care procedures such as (5) psychological integration and (6) supporting the development of structured patient communities. Definition of future treatment delivery infrastructures and requirements for therapist training are further challenges for research and practice. Finally, the implementation of psychedelic-assisted psychotherapy in routine mental health care must be embedded into public communication about the potential and risks of these innovative therapeutic approaches. This paper provides a synopsis of challenges for practitioners, researchers, and regulators to be addressed in the approval processes of psychedelics.

Patents on Psychedelics: The Next Legal Battlefront of Drug Development

In the past few decades, pioneering research has rekindled interest in the therapeutic use of psychedelic substances such as psilocybin, ibogaine, and dimethyltryptamine (DMT). Indigenous communities have used them for centuries, and researchers studied them in the 1950s and 60s. However, most psychedelics were banned in the 70s, when President Nixon launched the U.S. war on drugs. Fifty years later, rising rates of mental illness, substance use, and suicide are prompting researchers to revisit psychedelics, and some have gained permission to study them in limited quantities. Clinical trials are producing promising results, creating enthusiasm for commercializing and patenting psychedelics. This Essay analyzes the ethical, legal, and social implications of patenting these controversial substances. Patents on psychedelics raise unique concerns associated with their unusual qualities, history, and regulation. Because they were criminalized for decades, the Patent Office lacks personnel with expertise in the field, increasing the likelihood of granting meritless psychedelic patents. Moreover, because Indigenous communities pioneered many aspects of modern psychedelic therapies, their patenting by Western corporations may promote biopiracy, the exploitation of Indigenous knowledge without compensation. Importantly, control of psychedelics by a small number of companies may stifle innovation and reduce access to these therapies. The Essay presents proposals to reduce the risk of biopiracy and the issuance of meritless psychedelic patents. Potential solutions include the implementation of psychedelic patent pledges, the creation of psychedelic prior art repositories, and the tightening of patentability requirements for novel drug therapies. The Essay concludes that ultimately, due to their importance to the advancement of science and public health, psychedelics are appropriately viewed as research tools, eligible only for limited patent protection.

Toxicology and Analysis of Psychoactive Tryptamines.

Our understanding of tryptamines is poor due to the lack of data globally. Tryptamines currently are not part of typical toxicology testing regimens and their contribution to drug overdoses may be underestimated. Although their prevalence was low, it is increasing. There are few published data on the many new compounds, their mechanisms of action, onset and duration of action, toxicity, signs and symptoms of intoxication and analytical methods to identify tryptamines and their metabolites. We review the published literature and worldwide databases to describe the newest tryptamines, their toxicology, chemical structures and reported overdose cases. Tryptamines are 5-HT2A receptor agonists that produce altered perceptions of reality. Currently, the most prevalent tryptamines are 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT), 5-methoxy-N,N- diallyltryptamine (5-MeO-DALT) and dimethyltryptamine (DMT). From 2015 to 2020, 22 new analytical methods were developed to identify/quantify tryptamines and metabolites in biological samples, primarily by liquid chromatography tandem mass spectrometry. The morbidity accompanying tryptamine intake is considerable and it is critical for clinicians and laboratorians to be informed of the latest data on this public health threat.

DMT alters cortical travelling waves.

Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the 'precision-weighting of priors', thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.

Modulatory effects of ayahuasca on personality structure in a traditional framework

Ayahuasca is a psychoactive plant brew containing dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). It originates from the Amazon basin, where it is used primarily for ceremonial purposes. Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing, as well as spiritual growth.RationaleRecent evidence has shown that the similar acting psychedelic compound, psilocybin, facilitated long-term increases in trait openness following a single administration.ObjectivesThis paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca tourists.MethodWithin a mixed design, we examined the effect of ayahuasca on participants’ personality (measured by the NEO Personality Inventory 3 questionnaire) across time (pre- to post-ayahuasca administration, and 6-month follow-up), relative to a comparison group (who did not ingest ayahuasca).ResultsThe results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants, relative to the comparison group. Both of these changes were sustained at 6-month follow-up, and trait level increases were also observed in openness at this stage. Additionally, greater perceived mystical experience (measured using the Mystical Experience Questionnaire 30) was associated with increased reductions in neuroticism.ConclusionsThese findings, which indicate a positive mediating effect of ayahuasca on personality, support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics.

Biodiversity of β-Carboline Profile of Banisteriopsis caapi and Ayahuasca, a Plant and a Brew with Neuropharmacological Potential.

Ayahuasca is a psychoactive infusion with a large pharmacological application normally prepared with Banisteriopsis caapi, which contains the monoamine oxidase inhibitors β-carbolines, and Psichotria virids, which contains the serotonin receptor agonist N,N dimethyltryptamine (DMT). The objectives of this study were to investigate the chemical profile of B. caapi and of ayahuasca collected in various Brazilian regions. In total, 176 plant lianas, of which 159 B. caapi and 33 ayahuasca samples were analyzed. Dried liana samples were powdered, extracted with methanol, diluted, and analyzed by LC-MS/MS. Ayahuasca samples were diluted and analyzed. Mean concentrations in B. caapi were 4.79 mg/g harmine, 0.451 mg/g harmaline, and 2.18 mg/g tetrahydroharmine (THH), with a high variability among the samples (RSD from 78.9 to 170%). Native B. caapi samples showed significantly higher harmine concentrations than cultivated ones, and samples from the Federal District/Goiás had higher THH content than those collected in the State of Acre. The other Malpighiaceae samples did not contain β-carbolines, except for one D. pubipetala sample. Concentrations in ayahuasca samples ranged from 0.109 to 7.11 mg/mL harmine, 0.012 to 0.945 mg/mL harmaline, 0.09 to 3.05 mg/mL THH, and 0.10 to 3.12 mg/mL DMT. The analysis of paired ayahuasca/B. caapi confirmed that harmine is reduced to harmaline and to THH during the brew preparation. This is the largest study conducted with Malpighiaceae samples and showed a large variability in the main β-carbolines present in B. caapi. This biodiversity is a challenge for standardization of the material used in ethnopharmacological studies of B. caapi and ayahuasca.

Aspectos Farmacológicos e Toxicológicos do Alcaloide N, N – Dimetiltriptamina (DMT)

A N, N - dimetiltriptamina (DMT) é um alcaloide alucinógeno presente nas folhas de Psychotria viridis, uma planta muito utilizada em chás que são ingeridos durante determinados rituais religiosos, sendo o chá de Ayahuasca um dos mais conhecidos. Devido sua semelhança com o neurotransmissor serotonina (5-HT), a DMT age de forma agonista nos receptores serotoninérgicos 5-HT1A, 5-HT2A e 5-HT2C, causando diversos efeitos como náuseas, tremores e mudança de humor, alguns relatos apontam alterações no sistema imunológico devido à diminuição dos níveis de linfócitos CD3 e CD4. No entanto, pesquisas recentes apontam, também, os efeitos terapêuticos da DMT, comprovando através de testes in vivo seu potencial antitumoral, antidepressivo e ansiolítico, além de auxiliar no tratamento contra o alcoolismo e tabaco. Considerando o uso crescente de chás que contêm a DMT, esse trabalho tem como objetivo descrever seus principais efeitos farmacológicos e toxicológicos em virtude da limitação de referências e a necessidade de compilação de dados dispersos na literatura. O presente estudo conclui que a DMT possui potencial farmacológico, porém também importantes efeitos adversos, incluindo toxicidade, o que corrobora com a necessidade da realização de mais testes agudos e crônicos, além de pesquisas epidemiológicas focadas na sua ação nas populações que a usam.

Changes in field concentrations of five phalaris alkaloids and their association with toxicity in pastures of Victoria, Australia

Phalaris aquatica is known to cause toxicity in livestock in the form of acute or chronic staggers or sudden death neurological (SDN) syndrome. Breeding of cultivars that produce lower concentrations of suspected alkaloid toxins has been conducted, but these cultivars continue to cause staggers and SDN toxicity. Field samples of grazed phalaris pasture were collected during one growth season (February–June 2016), and from pastures where cases of staggers and/or SDN had occurred in previous years, and immediately after two cases of toxicity. Pasture collected from a paddock where a case of SDN occurred 4 days prior had elevated levels of 5-methoxy-N,N-dimethyltryptamine (5-MeO DMT) and slightly elevated levels of dimethyltryptamine (DMT) compared with other collections from the region. Pasture collected from a paddock at the time of a case of phalaris staggers did not have elevated levels of the quantified alkaloids. Across the measurement period, potentially toxic alkaloids gramine, hordenine, DMT and 5-MeO DMT were observed to decrease in concentration, whereas β-carboline (norharmane) was not detected in any sample. Excessive drying out of dormant plants was hypothesised to be a risk factor for phalaris toxicity. Continued management of potentially toxic phalaris pasture could include measures to manipulate the physiological processes that result in increased toxic alkaloids, including methods to reduce drying out of dormant phalaris plants, and managing stocking rates and grazing species to mitigate potential toxicity.

Effect of Sigma-1 Receptors on Voltage-Gated Sodium Ion Channels in Colon Cancer Cell Line SW620.

Background: Voltage-gated sodium channels (VGSCs) play pivotal roles in the metastatic process in several cancers, including breast and colon cancers. Sigma-1 receptors are known to interact and form complexes with a number of ion channels aiding the delivery of the channel protein to the plasma membrane. Drugs that bind the Sigma-1 receptor are hypothesized to affect this process and reduce the delivery of the channel protein to the plasma membrane, in turn reducing the metastatic potential of the cells. Methods: Human colon cancer cell line SW620 was utilized as a model to investigate the interaction between the neonatal VGSC (nNav1.5) and the Sigma-1 receptor. This was accomplished using drugs that bind the Sigma-1 receptor, Sigma-1 receptor silencing, and antibodies that bind and block the nNav1.5 channel. Results: Sigma-1 receptor drugs SKF10047 and dimethyl tryptamine were found to alter (reduce) the adhesion of these cells by 46-54% at a 20 μM drug concentration. In a similar manner, gene silencing of the Sigma-1 receptor had a similar effect in reducing the adhesion of these cells to collagen-coated plates by 30%. The Sigma-1 receptor was found to be in a complex with nNav1.5 in SW620 cells, and Sigma-1 drugs or gene silencing of the Sigma-1 receptor results in a reduction of the surface expression of nNav1.5 by ∼50%. Culture of SW620 cells under hypoxic conditions resulted in upregulation of the Sigma-1 receptor and nNav1.5. In addition, surface expression of nNav1.5 protein increased under hypoxic culture conditions and this was inhibited by the application of SKF10047. Conclusions: It is proposed that in colon cancer cells, upregulated Sigma-1 receptor expression in hypoxia led to increased nNav1.5 protein expression at the plasma membrane and resulted in the cells switching to a more invasive state.

Soma and Haoma: Ayahuasca analogues from the Late Bronze Age

In this article, the origins of the cult of the ritual drink known assoma/haomaare explored. Various shortcomings of the main botanical candidates that have so far been proposed for this so-called “nectar of immortality” are assessed. Attention is brought to a variety of plants identified assoma/haomain ancient Asian literature. Some of these plants are included in complex formulas and are sources of dimethyl tryptamine, monoamine oxidase inhibitors, and other psychedelic substances. It is suggested that through trial and error the same kinds of formulas that are used to make ayahuasca in South America were developed in antiquity in Central Asia and that the knowledge of the psychoactive properties of certain plants spreads through migrants from Central Asia to Persia and India. This article summarizes the main arguments for the botanical identity ofsoma/haoma, which is presented in my book,The Tawny One: Soma, Haoma and Ayahuasca(Muswell Hill Press, London/New York). However, in this article, all the topics dealt with in that publication, such as the possible ingredients of the potion used in Greek mystery rites, an extensive discussion of cannabis, or criteria that we might use to demarcate non-ordinary states of consciousness, have not been elaborated.

Comparing the detection of endogenous psychedelics in individuals with and without alleged mediumistic experiences

Context Mediumship is the alleged ability to communicate with deceased personalities. Previous studies have suggested that the endogenous psychotomimetic molecules bufotenine (BT) and dimethyltryptamine (DMT) may play a role in the pathogenesis of psychotic disorders. Distortion of perceptions observed during spiritual experiences could supposedly relate to these substances. Objective To compare the presence of BT and DMT in human urine samples between individuals with and without mediumistic experiences. Methods All participants (5 from medium's group - MG and 5 from non-medium's group - CG) undertook a single night continuous 6-h urine pool collection (6:00–11:59 PM). Mediums collected urine samples in nights when they reported having experienced mediumistic communication. A sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS) assay was used. Questionnaires were used to detect common mental disorders symptoms, and to screen and quantify anomalous experiences. Results DMT was not detected in any urine specimen tested. The presence of BT detection in urine samples was greater in CG (2/5) than in MG (1/5), with no significant differences (p > 0.99). MG reported more anomalous experiences than CG (6.6±0.8 vs. 2.2±1.5, p = 0.03), but there was no difference concerning their mental health. Conclusion There were no differences between individuals with and without alleged mediumistic experiences concerning endogenous psychedelics. Both BT and DMT are highly sensitive to metabolism by monoamine oxidase and to N-oxidation, and do not survive in the periphery for long. Alternative strategies should be considered to further investigate the putative role of the endogenous psychedelics pathway for the spiritual experiences.

Comparing the Detection of Endogenous Psychedelics in Individuals With and Without Alleged Mediumistic Experiences

Mediumship is the alleged ability to communicate with deceased personalities. Previous studies have suggested that the endogenous psychotomimetic molecules bufotenine (BT) and dimethyltryptamine (DMT) may play a role in the pathogenesis of psychotic disorders. Distortion of perceptions observed during spiritual experiences could supposedly relate to these substances. To compare the presence of BT and DMT in human urine samples between individuals with and without mediumistic experiences. All participants (5 from medium's group - MG and 5 from non-medium's group - CG) undertook a single night continuous 6-h urine pool collection (6:00-11:59PM). Mediums collected urine samples in nights when they reported having experienced mediumistic communication. A sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS) assay was used. Questionnaires were used to detect common mental disorders symptoms, and to screen and quantify anomalous experiences. DMT was not detected in any urine specimen tested. The presence of BT detection in urine samples was greater in CG (2/5) than in MG (1/5), with no significant differences (p > 0.99). MG reported more anomalous experiences than CG (6.6±0.8 vs. 2.2±1.5, p = 0.03), but there was no difference concerning their mental health. There were no differences between individuals with and without alleged mediumistic experiences concerning endogenous psychedelics. Both BT and DMT are highly sensitive to metabolism by monoamine oxidase and to N-oxidation, and do not survive in the periphery for long. Alternative strategies should be considered to further investigate the putative role of the endogenous psychedelics pathway for the spiritual experiences.

Dimetiltriptamina: alcalóide alucinógeno e seus efeitos no Sistema Nervoso Central

Plantas alucinógenas são bastante utilizadas em rituais e cultos religiosos. O chá de Ayahuasca e o vinho da Jurema preta, bebidas alucinógenas, apresentam o alcalóide dimetiltriptamina (DMT), responsável pelo efeito alucinógeno devido a interação com receptores serotoninérgicos no sistema nervoso central (SNC). O objetivo da pesquisa foi esclarecer os mecanismos de ação e os efeitos da DMT presente em bebidas alúcinógenas das espécies Mimosa tenuiflora (jurema preta), Banisteriopsis caapi (jagube ou cipó mariri) e Psychotria viridis (chacrona) sobre o SNC, elucidando os riscos da sua ingestão e informações sobre a legislação brasileira. O efeito alucinógeno ocorre a partir da interação dos receptores serotoninérgicos com DMT, esse estruturalmente semelhante a serotonina, o que interfere nas funções psíquicas, proporcionando modificações de dimensões, ilusões acústicas e ópticas, alterações no humor, distorção na percepção do tempo e espaço, despersonalização, midríase e hipertermia. Atualmente existe um acesso a essas substâncias e a difusão do seu uso está em expansão no Brasil, devido a relação com aspectos religiosos e culturais. Dessa forma, é importante conhecer os fatores que englobam o uso dessas substâncias, pois diversas alterações e complicações podem surgir a partir do uso, já que os efeitos alucinógenos provêm de interferências em funções fisiológicas.

The Role of Sigma-1 Receptor, an Intracellular Chaperone in Neurodegenerative Diseases.

Background:Widespread protein aggregation occurs in the living system under stress or during aging, owing to disturbance of endoplasmic reticulum (ER) proteostasis. Many neurodegenerative diseases may have a common mechanism: the failure of protein homeostasis. Perturbation of ER results in unfolded protein response (UPR). Prolonged chronical UPR may activate apoptotic pathways and cause cell death.Methods:Research articles on Sigma-1 receptor were reviewed.Results:ER is associated to mitochondria by the mitochondria-associated ER-membrane, MAM. The sigma-1 receptor (Sig-1R), a well-known ER-chaperone localizes in the MAM. It serves for Ca2+-signaling between the ER and mitochondria, involved in ion channel activities and especially important during neuronal differentiation. Sig-1R acts as central modulator in inter-organelle signaling. Sig-1R helps cell survival by attenuating ER-stress. According to sequence based predictions Sig-1R is a 223 amino acid protein with two transmembrane (2TM) domains. The X-ray structure of the Sig-1R [1] showed a membrane-bound trimeric assembly with one transmembrane (1TM) region. Despite the in vitro determined assembly, the results of in vivo studies are rather consistent with the 2TM structure. The receptor has unique and versatile pharmacological profile. Dimethyl tryptamine (DMT) and neuroactive steroids are endogenous ligands that activate Sig-1R. The receptor has a plethora of interacting client proteins. Sig-1R exists in oligomeric structures (dimer-trimer-octamer-multimer) and this fact may explain interaction with diverse proteins.Conclusion:Sig-1R agonists have been used in the treatment of different neurodegenerative diseases, e.g. Alzheimer’s and Parkinson’s diseases (AD and PD) and amyotrophic lateral sclerosis. Utilization of Sig-1R agents early in AD and similar other diseases has remained an overlooked therapeutic opportunity.

Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey

Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca’s subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca’s acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.

Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies.

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake.