The potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action.

Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic-assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4-12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5-MeO-DMT. Primarily, 5-MeO-DMT is able to induce mystical experiences and ego-dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood-related comorbidities consistent with the negative reinforcement and self-medication paradigms. In addition, preliminary evidence indicates that 5-MeO-DMT modulates neural oscillations that might subserve ego-dissolution (increases in gamma), psychological flexibility and mindfulness (increases in theta), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5-MeO-DMT is characterized by neuroplasticity, anti-inflammation, 5-HT2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood-related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action.

Trajectories of sentiment in 11,816 psychoactive narratives.

OBJECTIVE: Can machine learning (ML) enable data-driven discovery of how changes in sentiment correlate with different psychoactive experiences? We investigate by training models directly on text testimonials from a diverse 52-drug pharmacopeia. METHODS: Using large language models (i.e. BERT) and 11,816 publicly-available testimonials, we predicted 28-dimensions of sentiment across each narrative, and then validated these predictions with adjudication by a clinical psychiatrist. BERT was then fine-tuned to predict biochemical and demographic information from these narratives. Lastly, canonical correlation analysis linked the drugs' receptor affinities with word usage, revealing 11 statistically-significant latent receptor-experience factors, each mapped to a 3D cortical Atlas. RESULTS: These methods elucidate a neurobiologically-informed, sequence-sensitive portrait of drug-induced subjective experiences. The models' results converged, revealing a pervasive distinction between the universal psychedelic heights of feeling in contrast to the grim, mundane, and personal experiences of addiction and mental illness. Notably, MDMA was linked to "Love", DMT and 5-MeO-DMT to "Mystical Experiences" and "Entities and Beings", and other tryptamines to "Surprise", "Curiosity" and "Realization". CONCLUSIONS: ML methods can create unified and robust quantifications of subjective experiences with many different psychoactive substances and timescales. The representations learned are evocative and mutually confirmatory, indicating great potential for ML in characterizing psychoactivity.

Open-label study of consecutive ibogaine and 5-MeO-DMT assisted-therapy for trauma-exposed male Special Operations Forces Veterans: prospective data from a clinical program in Mexico.

Background: Research in psychedelic medicine has focused primarily on civilian populations. Further study is needed to understand whether these treatments are effective for Veteran populations.Objectives: Here, we examine the effectiveness of psychedelic-assisted therapy among trauma-exposed Special Operations Forces Veterans (SOFV) seeking treatment for cognitive and mental health problems in Mexico.Methods: Data were collected from an ibogaine and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) clinical treatment program for SOFV with a history of trauma exposure. This clinical program collects prospective clinical program evaluation data, such as background characteristics, symptom severity, functioning (e.g., satisfaction with life, posttraumatic stress disorder symptoms, depression symptoms, anxiety symptoms, sleep disturbance, psychological flexibility, disability in functioning, cognitive functioning, neurobehavioral symptoms, anger, suicidal ideation), and substance persisting/enduring effects through online surveys at four timepoints (baseline/pre-treatment, one-, three-, and six-months after treatment).Results: The majority of the sample (n = 86; Mean Age = 42.88, SD = 7.88) were Caucasian (87.2%), non-Hispanic (89.5%), and males (100%). There were significant and large improvements in self-reported PTSD symptoms (p < .001, d = .414), depression (p < .001, d = .275), anxiety (p < .001, d = .276), insomnia severity (p < .001, d = .351), and post-concussive symptoms (p < .001, d = .389) as well as self-reported satisfaction with life (p < .001, d = .371), psychological flexibility (p < .001, d = .313) and cognitive functioning (p < .001, d = .265) from baseline to one-month follow-up.Conclusions: Data suggest combined ibogaine and 5-MeO-DMT assisted therapy has potential to provide rapid and robust changes in mental health functioning with a signal of durable therapeutic effects up to 6-months. Future research in controlled settings is warranted.

"In vivo biosynthesis of N,N-dimethyltryptamine, 5-MeO-N,N-dimethyltryptamine, and bufotenine in E.coli".

N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and 5-hydroxy-N,N-dimethyltryptamine (bufotenine) are psychedelic tryptamines found naturally in both plants and animals and have shown clinical potential to help treat mental disorders, such as anxiety and depression. Advances in both metabolic and genetic engineering make it possible to engineer microbes as cell factories to produce DMT and its aforementioned derivatives to meet demand for ongoing clinical study. Here, we present the development of a biosynthetic production pathway for DMT, 5-MeO-DMT, and bufotenine in the model microbe Escherichia coli. Through the application of genetic optimization techniques and process optimization in benchtop fermenters, the in vivo production of DMT in E. coli was observed. DMT production with tryptophan supplementation reached maximum titers of 74.7 ± 10.5 mg/L under fed batch conditions in a 2-L bioreactor. Additionally, we show the first reported case of de novo production of DMT (from glucose) in E. coli at a maximum titer of 14.0 mg/L and report the first example of microbial 5-MeO-DMT and bufotenine production in vivo. This work provides a starting point for further genetic and fermentation optimization studies with the goal to increase methylated tryptamine production metrics to industrially competitive levels.

5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice.

Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early phase clinical studies. However, relatively little is known about the behavioral and neural mechanisms of 5-MeO-DMT, particularly the durability of its long-term effects. Here we characterized the effects of 5-MeO-DMT on innate behaviors and dendritic architecture in mice. We showed that 5-MeO-DMT induces a dose-dependent increase in head-twitch response that is shorter in duration than that induced by psilocybin at all doses tested. 5-MeO-DMT also substantially suppresses social ultrasonic vocalizations produced during mating behavior. 5-MeO-DMT produces long-lasting increases in dendritic spine density in the mouse medial frontal cortex that are driven by an elevated rate of spine formation. However, unlike psilocybin, 5-MeO-DMT did not affect the size of dendritic spines. These data provide insights into the behavioral and neural consequences underlying the action of 5-MeO-DMT and highlight similarities and differences with those of psilocybin.

Interaction of psychedelic tryptamine derivatives with a lipid bilayer.

Naturally occurring psychedelics have been used for a long time as remedies or in religious ceremonies and recreational activities. Recent studies have proven the therapeutic potential of some psychedelic compounds to safely treat a wide range of diseases such as anxiety, depression, migraine, and addiction. It is hypothesized that psychedelic compounds like tryptamines can exert their effects by two possible mechanisms: binding to the transmembrane serotonin receptor and/or modifying the properties of the neuronal membrane that can alter the conformational equilibrium and desensitize receptors. The impact of three different tryptamine class compounds with a tertiary amine (dimethyltryptamine, bufotenine, and 5-MeO-DMT) in both neutral and charged forms on a model bilayer lipid membrane are studied using all-atom MD simulations. All compounds partition into the bilayer, and change membrane properties, but to different extents. We determine the tendency of compounds to partition into the membrane by free energy calculations. Neutral tryptamines partition into the bilayer almost completely. Dimethyltryptamine and 5-MeO-DMT cross the membrane spontaneously during the simulation time, but bufotenine does not, although it has the maximum effect on the structural properties of the membrane. However, protonated compounds partition partially into the bilayer and cannot pass through the middle of the membrane during the simulation time. In this way, subtle alteration of chemical structure can play a significant role in the improvement or deterioration of partitioning of these compounds into the bilayer and their passage across the membrane.

Molecular Docking, MM-GBSA, and Molecular Dynamics Approach: 5-MeO-DMT Analogues as Potential Antidepressants.

Since depression is a common mental illness affecting an estimated 5% of people worldwide, investigators are encouraged to develop effective antidepressants. According to the monoamine-deficiency hypothesis, the underlying pathophysiology of depression is a deficiency of some neurotransmitters (serotonin, norepinephrine, or dopamine) in the central nervous system. The neurotransmitter serotonin has drawn the most attention concerning depression. As per research, 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) elevates inter-synaptic serotonin levels when administered as a single inhalation of vapor from dried toad secretion and leads to higher life satisfaction, convergent thinking, higher ratings of mindfulness, lower ratings of depression, and anxiety. Furthermore, although 5-MeO-DMT lowers stress biomarkers such as cortisol, it is a psychedelic with hallucinogenic effects. In the present study, analogues of 5-MeO-DMT are designed with the hope that they might have better therapeutic activity and lower psychedelic side effects. The current study aimed to look at 5-MeO-DMT analogues as possible antidepressants. We used 70,000 5-MeO-DMT analogues that were sketched using Marvin to conduct a High Throughput Virtual Screening method in hopes of finding potential 5-MeO-DMT analogues against the 5-Hydroxytryptamine 1A receptor (5-HT1AR; 7E2Y.pdb) as an agonist. The prediction of the analogue-protein interaction and the evaluation of the binding affinity is accomplished by employing molecular docking. The Glide XP docking data indicated that a total of 21 compounds had Glide gscores ranging from -11.41 to -6.53 kcal/mol. When compared to the standard 5-MeO-DMT with the binding affinity of -7.75 kcal/mol, 14 compounds showed better binding affinity. Furthermore, Molecular Mechanics -Generalised Born and Surface Area solvation (MM-GBSA) indicated a binding free energy range of -63.55 to -35.37 kcal/mol, and 18 compounds showed better binding free energy than standard 5-MeO-DMT (-41.42 kcal/mol). Through ligand binding interactions with Asp116, Phe361, Phe362, Ser190, Ser199, Val117, Trp358, Ala365, Pro369, Ile189, Tyr195, Ala203, Ile167, Tyr390, Cys120, Trp358, Val364, Ala365, and Leu368, these complexes were stabilized, according to the molecular dynamic simulation of 20453/7E2Y in 100ns.

LC-MS/MS-based metabolomics approach revealed novel phytocompounds from sugarcane rind with promising pharmacological value.

BACKGROUND: Sugarcane provides many secondary metabolites for the pharmacological and cosmetic industries. Secondary metabolites, such as phenolic compounds, flavonoids, and anthocyanins, have been studied, but few reports focus on the identification of alkaloid and non-alkaloid phytocompounds in sugarcane. RESULTS: In this study, we identified 40 compounds in total from the rinds of cultivated sugarcane varieties (including eight alkaloids, 24 non-alkaloids, and eight others) by using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach. Among these compounds, 31 were novel and are reported for the first time in sugarcane. Some alkaloids such as 3-indoleacrylic acid, N,N-dimethyl-5-methoxytryptamine, tryptamine, 6-hydroxynicotinic acid, and 6-deoxyfagomine are identified the first time in sugarcane rind. Four alkaloids such as trigonelline, piperidine, 3-indoleacrylic acid, and 6-deoxyfagomine are found abundantly in sugarcane rind and these compounds have promising pharmaceutical value. Some phytocompounds such as choline and acetylcholine (non-alkaloid compounds) were most common in the rind of ROC22 and Yuetang93/159 (YT93/159). Hierarchical cluster analysis and principal component analysis revealed that the ROC22, Taitang172 (F172), and Yuetang71/210 (YT71/210) varieties were quite similar in alkaloid composition when compared with other sugarcane varieties. We have also characterized the biosynthesis pathway of sugarcane alkaloids. The rind of F172, ROC22, and YT71/210 showed the highest total alkaloid content, whereas the rind of ROC16 revealed a minimum level. Interestingly, the rind extract from YT71/210 and F172 showed maximum antioxidant activity, followed by ROC22. CONCLUSION: Our results showed the diversity of alkaloid and non-alkaloid compounds in the rind of six cultivated sugarcanes and highlighted the promising phytocompounds that can be extracted, isolated, and utilized by the pharmacological industry. © 2022 Society of Chemical Industry.

The clinical pharmacology and potential therapeutic applications of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT).

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring tryptamine that primarily acts as an agonist at the 5-HT1A and 5-HT2A receptors, whereby affinity for the 5-HT1A subtype is highest. Subjective effects following 5-MeO-DMT administration include distortions in auditory and time perception, amplification of emotional states, and feelings of ego dissolution that usually are short-lasting, depending on the route of administration. Individual dose escalation of 5-MeO-DMT reliably induces a "peak" experience, a state thought to be a core predictor of the therapeutic efficacy of psychedelics. Observational studies and surveys have suggested that single exposure to 5-MeO-DMT can cause rapid and sustained reductions in symptoms of depression, anxiety, and stress. 5-MeO-DMT also stimulates neuroendocrine function, immunoregulation, and anti-inflammatory processes, which may contribute to changes in mental health outcomes. To date, only one clinical trial has been published on 5-MeO-DMT, demonstrating the safety of vaporized dosing up to 18 mg. Importantly, the rapid onset and short duration of the 5-MeO-DMT experience may render it more suitable for individual dose-finding strategies compared with longer-acting psychedelics. A range of biotech companies has shown an interest in the development of 5-MeO-DMT formulations for a range of medical indications, most notably depression. Commercial development will therefore be the most important resource for bringing 5-MeO-DMT to the clinic. However, fundamental research will also be needed to increase understanding of the neurophysiological and neural mechanisms that contribute to the potential clinical effects of 5-MeO-DMT and its sustainability and dissemination over time. Such studies are less likely to be conducted as part of drug development programs and are more likely to rely on independent, academic initiatives.

A narrative synthesis of research with 5-MeO-DMT.

BACKGROUND: 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring, short-acting psychedelic tryptamine, produced by a variety of plant and animal species. Plants containing 5-MeO-DMT have been used throughout history for ritual and spiritual purposes. The aim of this article is to review the available literature about 5-MeO-DMT and inform subsequent clinical development. METHODS: We searched PubMed database for articles about 5-MeO-DMT. Search results were cross-checked against earlier reviews and reference lists were hand searched. Findings were synthesised using a narrative synthesis approach. This review covers the pharmacology, chemistry and metabolism of 5-MeO-DMT, as well epidemiological studies, and reported adverse and beneficial effects. RESULTS: 5-MeO-DMT is serotonergic agonist, with highest affinity for 5-HT1A receptors. It was studied in a variety of animal models, but clinical studies with humans are lacking. Epidemiological studies indicate that, like other psychedelics, 5-MeO-DMT induces profound alterations in consciousness (including mystical experiences), with potential beneficial long-term effects on mental health and well-being. CONCLUSION: 5-MeO-DMT is a potentially useful addition to the psychedelic pharmacopoeia because of its short duration of action, relative lack of visual effects and putatively higher rates of ego-dissolution and mystical experiences. We conclude that further clinical exploration is warranted, using similar precautions as with other classic psychedelics.

Qualitative and Quantitative Analysis of Tryptamines in the Poison of Incilius alvarius (Amphibia: Bufonidae).

Rising numbers of psychoactive tryptamine derivatives have become available on the drug market over the last decade, making these naturally occurring or synthetically manufactured compounds highly relevant for forensic analyses. One of these compounds is 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a constituent of the dried poison of Incilius alvarius (Colorado River toad), which has a history of ritual and/or recreational use. Still, comprehensive and validated qualitative as well as quantitative analytical data on the psychoactive components of this poison are scarce. In this study, samples of the poison of Incilius alvarius were collected from live toads in the Sonoran Desert, Arizona (USA), and analyzed with a set of complementary methods. Acetone/water (70/30, v/v) proved to be the solvent of choice for the extraction of tryptamine derivatives. Trace compounds were enriched, and overload with 5-MeO-DMT was prevented by chromatographic separation of 5-MeO-DMT prior to qualitative analyses. The method for quantification was validated. Attenuated total reflection-Fourier transform infrared spectroscopy was suitable to identify 5-MeO-DMT as the main tryptamine in samples of the poison. The combined evaluation of analytical data gained from gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography-quadrupole time-of-flight high-resolution MS (HPLC-qToF-HRMS) and HPLC-MS-MS confirmed the presence of 5-MeO-DMT, 5-MeO-N-methyltryptamine, 5-MeO-tryptamine, 5-MeO-tryptophol, 2-(5-methoxy-1H-indol-3-yl)-acetic-acid (5-MIAA), 5-HO-N-methyltryptamine, bufotenin, DMT and tryptophan. For the first time, 5-MeO-tryptamine and two positional isomers of hydroxylated MeO-DMT were detected in the poison of Incilius alvarius. The tryptamine present in the highest concentrations was 5-MeO-DMT (mean ± SD: 410,000 ± 30,000 µg/g). Mean concentrations of 5-MeO-tryptamine (490 ± 260 µg/g), 5-HO-N-methyltryptamine (270 ± 120 µg/g), bufotenin (2,800 ± 1,900 µg/g) and DMT (250 ± 80 µg/g) showed a relatively high variability between individual samples. The comprehensive analytical reference data of Incilius alvarius poison presented here might prove useful for forensic chemists.

Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MeO-DMT.

Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. We also tested whether a single dose of DMT can prevent this effect. Using microwire electrode arrays, we recorded local field potential in young (4-5- month-old) and old (11-13-month-old) mice to study the electrophysiological effect of tinnitus in the ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in an open field arena and elevated plus maze 1h after salicylate (300mg/kg) injection. We found that anxiety-like behavior and increase in theta2 oscillations (4-6 Hz), following salicylate pre-treatment, only occurs in young (normal hearing) mice. We also show that theta2 and slow gamma oscillations increase in the vHipp and mPFC in a complementary manner during anxiety tests in the presence of salicylate. Finally, we show that pre-treating mice with a single dose of the hallucinogenic 5-MeO-DMT prevents anxiety-like behavior and the increase in theta2 and slow gamma oscillations after salicylate injection in normal hearing young mice. This work further support the hypothesis that anxiety-like behavior after salicylate injection is triggered by tinnitus and require normal hearing. Moreover, our results show that hallucinogenic compounds can be effective in treating tinnitus-related anxiety.

A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms.

BACKGROUND: 5-methoxy-N,N-dimethyltryptamine (hereinafter referred to as 5-MeO-DMT) is a psychedelic substance found in the secretion from the parotoid glands of the Bufo alvarius toad. Inhalation of vapor from toad secretion containing 5-MeO-DMT has become popular in naturalistic settings as a treatment of mental health problems or as a means for spiritual exploration. However, knowledge of the effects of 5-MeO-DMT in humans is limited. AIMS: The first objective of this study was to assess sub-acute and long-term effects of inhaling vapor from dried toad secretion containing 5-MeO-DMT on affect and cognition. The second objective was to assess whether any changes were associated with the psychedelic experience. METHODS: Assessments at baseline, within 24 h and 4 weeks following intake, were made in 42 individuals who inhaled vapor from dried toad secretion at several European locations. RESULTS: Relative to baseline, ratings of satisfaction with life and convergent thinking significantly increased right after intake and were maintained at follow-up 4 weeks later. Ratings of mindfulness also increased over time and reached statistical significance at 4 weeks. Ratings of depression, anxiety, and stress decreased after the session, and reached significance at 4 weeks. Participants that experienced high levels of ego dissolution or oceanic boundlessness during the session displayed higher ratings of satisfaction with life and lower ratings of depression and stress. CONCLUSION: A single inhalation of vapor from dried toad secretion containing 5-MeO-DMT produces sub-acute and long-term changes in affect and cognition in volunteers. These results warrant exploratory research into therapeutic applications of 5-MeO-DMT.

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety.

BACKGROUND: A recent epidemiological study suggested that 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used for spiritual and recreational reasons is associated with subjective improvement in depression and anxiety. Further exploration of the potential psychotherapeutic effects of 5-MeO-DMT could inform future clinical trials. OBJECTIVES: We examined self-reported improvement in depression and anxiety among people who use 5-MeO-DMT in a group setting with structured procedures guiding dose and administration of 5-MeO-DMT. Such procedures also include activities for the preparation of, and support during/following sessions, which are similar to procedures used in clinical trials of hallucinogen administration. Next, we examined whether depression or anxiety were improved following use, and whether the acute subjective effects (mystical/challenging) or beliefs about the 5-MeO-DMT experience were associated with improvements in these conditions. METHODS: Respondents (n = 362; Mage = 47.7; Male = 55%; White/Caucasian = 84%) completed an anonymous web-based survey. RESULTS: Of those reporting having been diagnosed with depression (41%) or anxiety (48%), most reported these conditions were improved (depression = 80%; anxiety = 79%) following 5-MeO-DMT use, and fewer reported they were unchanged (depression = 17%; anxiety = 19%) or worsened (depression = 3%; anxiety = 2%). Improvement in depression/anxiety conditions were associated with greater intensity of mystical experiences and higher ratings of the spiritual significance and personal meaning of the 5-MeO-DMT experience. There were no associations between depression or anxiety improvement and the intensity of acute challenging physical/psychological effects during the 5-MeO-DMT experience. CONCLUSIONS: Future prospective controlled clinical pharmacology studies should examine the safety and efficacy of 5-MeO-DMT administration for relieving depression and anxiety.

A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder.

Ibogaine is a plant-derived alkaloid and dissociative psychedelic that demonstrates anti-addictive properties with several substances of abuse, including alcohol. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring psychedelic known to occasion potent mystical-type experiences and also demonstrates anti-addictive properties. The potential therapeutic effects of both compounds in treating alcohol use disorder require further investigation and there are no published human neuroimaging findings of either treatment to date. We present the case of a 31-year-old male military veteran with moderate alcohol use disorder who sought treatment at an inpatient clinic in Mexico that utilized a sequential protocol with ibogaine hydrochloride (1550mg, 17.9mg/kg) on day 1, followed by vaporized 5-MeO-DMT (bufotoxin source 50mg, estimated 5-MeO-DMT content, 5-7mg) on day 3. The patient received SPECT neuroimaging that included a resting-state protocol before, and 3 days after completion of the program. During the patient's ibogaine treatment, he experienced dream-like visions that included content pertaining to his alcohol use and resolution of past developmental traumas. He described his treatment with 5-MeO-DMT as a peak transformational and spiritual breakthrough. On post-treatment SPECT neuroimaging, increases in brain perfusion were noted in bilateral caudate nuclei, left putamen, right insula, as well as temporal, occipital, and cerebellar regions compared to the patient's baseline scan. The patient reported improvement in mood, cessation of alcohol use, and reduced cravings at 5 days post-treatment, effects which were sustained at 1 month, with a partial return to mild alcohol use at 2 months. In this case, serial administration of ibogaine and 5-MeO-DMT resulted in increased perfusion in multiple brain regions broadly associated with alcohol use disorders and known pharmacology of both compounds, which coincided with a short-term therapeutic outcome. We present theoretical considerations regarding the potential of both psychedelic medicines in treating alcohol use disorders in the context of these isolated findings, and areas for future investigation.

The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption.

BACKGROUND/AIM: 5-Methoxy- N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in several plants and in high concentrations in Bufo alvarius toad venom. Synthetic, toad, and plant-sourced 5-MeO-DMT are used for spiritual and recreational purposes and may have psychotherapeutic effects. However, the use of 5-MeO-DMT is not well understood. Therefore, we examined patterns of use, motivations for consumption, subjective effects, and potential benefits and consequences associated with 5-MeO-DMT use. METHODS: Using internet-based advertisements, 515 respondents ( Mage=35.4. SD=11.7; male=79%; White/Caucasian=86%; United States resident=42%) completed a web-based survey. RESULTS: Most respondents consumed 5-MeO-DMT infrequently (