How can dmt be made

Citations 1. Abstract High Resolution Image. Recently, interest has increased in understanding the clinical applications of psychedelic, entactogenic, and dissociative psychoactive drugs, such as psilocybin 1 , DMT 2 , LSD 3 , MDMA 4 , or ketamine 5 in combination with psychotherapeutic support to promote improved mental health conditions Figure 1.

These factors include the intensity of mystical experience occasioned by the psychedelic, the context in which the session was conducted known as set and setting , the dose at which the drug is administered, psychological flexibility, connectedness, emotional breakthrough, and increased neural entropy.

High Resolution Image. Human consumption of this material for its psychoactive properties has been reported in the scientific literature for at least years. Anecdotally, and suggested by research over the last 5 years, 5-MeO-DMT has been reported to be helpful in treating clinical mental health conditions.

An extensively supported hypothesis is that commonly encountered psychedelic effects in humans e. While a number of potential mechanisms have been hypothesized to rationalize the therapeutic mode of action of psychedelics, such as increased structural plasticity in the prefrontal cortex, 32 still no direct connection has been made between specific psychedelic pharmacodynamics and positive therapeutic outcomes. Unlike psilocybin, psychedelic tryptamines such as DMT 2 and 5-MeO-DMT 6 are subject to rapid first-pass metabolism by monoamine oxidase and are therefore not orally active.

When consumed parenterally, they produce a significantly shorter duration of action, typically less than 1 h, compared to the 5—8 h duration of effects produced by psilocybin. The shorter duration of action may help in reducing the amount of time a patient would spend in the clinic. These features may correlate with more positive therapeutic outcomes in controlled human clinical trials.

To test this hypothesis and to better understand the psychotherapeutic utility of 5-MeO-DMT and enable such clinical trials, the preparation of active pharmaceutical ingredient API is required with adequate controls to ensure its identity, potency, purity, and strength.

The development of this process is the topic of this report. Results and Discussion. The most commonly reported route of administration is by vaporization of the freebase drug, which is generally not a pharmaceutically acceptable approach compared to other dosage forms. While other intraperitoneal routes of administration with 5-MeO-DMT such as dry powder inhalation, transdermal, or intravenous administration are possible, an intramuscular injection has been identified as a preferable compromise for administering this material.

In addition to allowing precise metering of dose, the intramuscular injection of 5-MeO-DMT in a naturalistic setting has been previously reported and was claimed to possess an advantageous duration of action compared to the intense rapid-onset produced by other intraperitoneal routes. In parallel to the exploration of viable synthetic routes to 5-MeO-DMT freebase, a range of pharmaceutically acceptable salt forms were considered from acids with sufficient p K a difference to fully protonate 6 , including the counterions chloride, sulfate, fumarate, succinate, maleate, lysate, oxalate, benzoate, tartrate, mesylate, or acetate.

Attempts at formation of the sulfate salt yielded an intractable gum and the approach was abandoned. The hydrochloride salt was readily prepared as an apparent crystalline solid, but the material was found to be hygroscopic and was deliquescent under high-humidity conditions.

Both the fumarate and succinate salts were readily prepared and provided stable, free-flowing, crystalline materials. The fumarate salts of structurally analogous tryptamines are commonly reported, possibly due to their ease of synthesis. Succinic acid is a structurally similar dicarboxylic acid but lacks the conjugated double bond present in fumaric acid and would not exhibit similar chemical reactivity. The succinate salt was therefore explored further as a potential pharmaceutically acceptable salt form.

Briefly, 5-MeO-DMT succinate was not hygroscopic and XRPD indicated that multiple crystallization conditions resulted in a common stable crystalline anhydrate form A with only a few conditions that formed unique solvated forms see the Supporting Information. The data supported the use of 5-MeO-DMT succinate as a stable and pharmaceutically acceptable salt form. Given its ease of synthesis and favorable solid-state properties, this salt form was selected for further development.

For clinical development, the ideal synthetic route to 5-MeO-DMT would utilize commercially available starting materials, would be scalable to readily provide the product in the range of 0. The literature survey revealed three potentially viable synthetic routes, and each was explored and evaluated for the ability to meet the above criteria.

A seemingly attractive single-step process employed a modified Eschweiler—Clarke reaction via reductive amination between formaldehyde and commercially available 5-methoxy tryptamine 7 with sodium cyanoborohydride as the reducing agent Scheme 1.

Though product formation was evident, the reaction was plagued by challenges that would likely multiply at larger scales. The Pictet—Spengler reaction to the corresponding tryptoline 8 was difficult to suppress and removal of this structurally similar and possibly biologically active byproduct was challenging. Further optimization to Route 1 may be possible, but ultimately, the reaction was not recommended for further development.

A related reaction involving N-methylation of tryptamine 7 by methyl iodide has also been suggested; however, this approach would inevitably lead to difficult-to-control quaternization at the amine and was therefore also not considered for large-scale synthesis.

Scheme 1. The Speeter—Anthony tryptamine synthesis Scheme 2 is the most cited general method for preparing substituted psychedelic tryptamines and has also been used to prepare 5-MeO-DMT previously.

Crookes et al. Therefore, a single-step procedure based on the Fischer indole reaction was next explored. Scheme 2. Several attributes inherent to the Fischer indole reaction approach to 6 from 4-methoxyphenylhydrazine 13 and 4,4-diethoxy- N , N -dimethylbutanamine 14 , a masked aldehyde protected as the diethyl acetal derivative Scheme 3 A , were attractive for the development of a scalable process: the transformation occurs in a single step, it does not rely on high temperatures, occurs in aqueous solvent, and does not rely on air-sensitive or pyrophoric reactants such as lithium aluminum hydride.

Additionally, literature precedent exists for its use specifically in the synthesis of 5-MeO-DMT in addition to related substituted N , N -dimethyltryptamines, 46 with reported examples for the use of an analogous process in the commercial manufacture of structurally similar 5-substituted dimethyltryptamine antimigraine medicines, such as sumatriptan 15 , zolmitriptan 16 , and rizatriptan 17 Scheme 3 B.

Scheme 3. As per the previously published protocol, the reaction was first conducted in refluxing dilute aqueous sulfuric acid solution Table 1 , entry 1. With the significant impurity profile, the reaction would have likely required chromatography to isolate the product of sufficient purity. Serendipitously, we observed that an aliquoted LCMS sample removed prior to reflux prepared in acetonitrile instead of water proceeded to near completion at or below room temperature and contained almost exclusively 6 with few byproducts.

Based on the encouraging results, the process was repeated, and additional conditions were explored. Table 1.

Reaction Optimization Conditions. To better understand the role of the cosolvent, several additional reactions were trialed with different cosolvents, including methanol, dimethyl sulfoxide DMSO , 2-methyltetrahydrofuran 2-MeTHF , and dichloromethane DCM Table 1 , entries 4—7 compared to the same volume of only water under otherwise identical conditions Table 1 , entry 8.

The results indicated that all cosolvents tested were advantageous in increasing reaction conversion, with water-miscible polar aprotic DMSO providing results comparable to that of acetonitrile. Methanol also exhibited a significant enhancing effect on the reaction. These data indicated that most cosolvents improved the conversion and purity profile of the reaction, and the water-miscible polar aprotic cosolvents demonstrated a significant rate-enhancing effect and minimized side reactions in the formation of 6.

Though both reactants 13 and 14 appeared to be water soluble in the absence of cosolvent, we hypothesized that the addition of cosolvent possibly assisted in solubilizing either reactant or prevented the formation of hydrophobic clusters.

The hypothesis is supported by the observation that in the absence of cosolvent, the major side reaction impurities formed were indicative of high-molecular-weight oligomers, which could potentially form from localized high-concentration clusters of starting reactants.

Though DMSO and acetonitrile performed comparably, acetonitrile was selected for further development as the high-boiling point and low volatility of DMSO may have introduced additional complexity by its eventual removal in the workup. Further optimization revealed that diethyl acetal 14 could be reduced to 1. On larger-scale reactions where extended hold times of the freebase product in methylene chloride were required, formation of a heavy insoluble oil impurity was encountered.

The crude heavy oil was analyzed by 1 H NMR, which provided a singlet at 5. The apparent reactivity between product 6 and dichloromethane indicated that an alternative solvent should be used in the workup process, especially at larger scales where extended hold times may be required.

Scheme 4. Additionally, 2-MeTHF represented a greener solvent choice for process chemistry, as it is produced industrially by biorenewable processes. On smaller scales, the acetonitrile cosolvent was distilled prior to workup. On larger scales, this distillation was avoided and the workup proceeded directly into a liquid—liquid washing step.

Subsequent data would indicate that some product loss occurred in the first washing step by being extracted into the organic phase, possibly related to increased partitioning due to the acetonitrile present. Though ethanol was initially identified as a suitable recrystallization solvent for the succinate salt of 6 , the isomeric dimers were found to co-crystallize with 6 at levels that exceeded impurity specifications. Alternatively, we speculated that a significant differential in retention would exist between monoamine 6 and triamine isomers of 19 on silica gel, such that a filtration through a small silica plug would be sufficient to remove the polar impurities while allowing the product 6 to readily elute.

Scheme 5. The degradant was conclusively identified as oxidation degradant 21 , the N -oxide of 6. Previous in vitro and in vivo metabolism data has indicated that N-oxide 21 is a metabolite of 6 54 and would therefore afford some flexibility in the allowable levels of this degradant in the API. Scheme 6. Synthesis of N-Oxide With smaller-scale development reactions, the succinic acid salt of 6 was readily isolated by adding 1 equiv of succinic acid to a solution of freebase 6 in acetone and collecting the resulting insoluble crystalline precipitate by filtration.

We later found that the inclusion of a washing step using activated charcoal helped to minimize slight variability in color observed in the final isolated product. The procedure was modified to form the succinate salt in a solution of methanol at a volume that did not initially induce precipitation. The resulting solution was stirred with activated charcoal, filtered, and then concentrated. The resulting solid succinate salt was slurried in acetone, filtered, and dried to provide a crystalline solid consistent with the desired polymorphic form.

The identified N-oxide degradant 21 was the only detectable impurity at 0. Though not reported in the larger-scale synthesis, as the required purity specifications were met, following salt formation, ethanol was found to perform well as a recrystallization solvent for further purification of the succinate salt of 6 if necessary.

The Fischer indole reaction to 6 readily provided API that met all set specifications. Achieving a high-purity product was the initial focus, and further optimization could improve the final yield without compromising final product purity. In the future, the washes could potentially be back-extracted to recover this loss. With further scale-up, the elimination of the silica pad filtration step would be desirable.

Vacuum distillation of the crude freebase could be an acceptable alternative for the separation of the freebase product from high-MW dimers such as Though dimer impurities present in succinate salt were not readily purged by recrystallization approaches, exploration of the recrystallization of alternate salt forms prior to generation of the succinate salt may also circumvent the silica pad filtration. As an alternative to purification approaches, additional optimization of reaction conditions could be explored to further improve the specificity of the reaction toward formation of 6 and minimize side reactions.

The first production run has provided sufficient API to meet current clinical and nonclinical needs to enable first-in-human clinical trials with 6. The key features of the developed process were an optimized Fischer indole reaction with advantageous inclusion of acetonitrile cosolvent to provide crude freebase 6. The workup featured greener solvent choices with an intermediate purification via filtration through a silica pad. The succinic acid salt was subsequently prepared from methanol with an activated charcoal decolorizing step followed by final purification by acetone slurry.

A minor API degradation product, the corresponding N-oxide 21 , was identified, synthesized, and characterized. The controllability and scalability inherent to the developed process will ensure that current and future clinical demands for 6 are met.

Experimental Section. Reactions were performed using commercially obtained raw materials and solvents. Unless otherwise stated, all commercially obtained reagents were identity tested and used as received. Reactions were conducted in a Borosilicate Glass 3. Chromatographic peaks were detected by a diode array detector at nm. Low and high collision energy mass spectra were acquired using a Waters MSe experiment.

To a clean and dry 5 L reactor was charged 4-methoxyphenylhydrazine hydrochloride To the suspension, concentrated H 2 SO 4 Note: This addition is slightly exothermic. A solution of 4,4-diethoxy- N , N -dimethylbutanamine 14 The addition funnel was rinsed with acetonitrile mL, 1. Result: 4-Methoxyphenylhydrazine: 1. After each wash, the layers were allowed to settle for 15 min. The lower acidic aqueous layer was collected and the upper 2-MeTHF wash was discarded. The acidic aqueous layer was recharged to the reactor and sodium hydroxide solution 4 M, 0.

The lower aqueous layer was discarded and the combined 2-MeTHF organic layers were transferred to a 20 L-flask. The solution was concentrated in vacuo to an oily amber residue. Residual water was removed azeotropically by redissolving the residue with fresh 2-MeTHF 1. The crude freebase was dissolved in acetone 1.

The combined filtrates were concentrated to provide The flask was attached to a rotary evaporator and rotation was started without applying vacuum until the material dissolved. The methanolic solution was then transferred to a 5 L-RBF fitted with an overhead mechanical stirrer.

Additional MeOH 2. Succinic acid The Celite pad was rinsed with additional MeOH 3. The collected filtrate 5. Acetone was charged in portions to the rotatory evaporator containing the solid 5-MeO-DMT succinate salt and the solvent concentrated until no more distillate was observed to ensure that most of the residual MeOH had been distilled. Fresh acetone Freebase 6 mg, 2. Ethanol ca. Supporting Information. Author Information. Alexander M.

Kristi W. The authors declare no competing financial interest. Clinical Applications of Hallucinogens: A Review. American Psychological Association. Hallucinogens fall into several different classes, as broadly defined by pharmacol.

These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse.

This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clin. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the mol. Expert Rev. A review. This review discusses the role of hallucinogens for treating mental illness. This development of novel approaches to treating mental illness is discussed.

The hallucinogens are used to treat diseases such as severe post-traumatic stress disorder, depression, anxiety, etc. The success of hallucinogen-based therapies will depend on the application of ethically sound and rigorous scientific methods towards the continued demonstration of significant clin. Psychopharmacology , , — , DOI: Carhart-Harris, R. Rationale: Recent clin. Objectives: Here, we report on safety and efficacy outcomes for up to 6 mo in an open-label trial of psilocybin for treatment-resistant depression.

Methods: Twenty patients six females with mostly severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin 10 and 25 mg, 7 days apart in a supportive setting.

Depressive symptoms were assessed from 1 wk to 6 mo post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure.

Results: Treatment was generally well tolerated. Relative to baseline, marked redns. Results remained pos. No patients sought conventional antidepressant treatment within 5 wk of psilocybin. Conclusions: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 mo post-treatment in a treatment-resistant cohort.

Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomized control trials. As discussed and delineated above, more research is needed on DMT's natural role and function and interaction with other neurotransmitter systems.

This will require the recommended future research into DMT biosynthesis, metabolism and binding, new methods for peripheral and central detection and data from administration, imaging and therapeutic trial studies. The data derived from the areas of research addressed above will no doubt suggest several possible new avenues for additional future research on DMT. In order to advance, however, regulatory blockades to hallucinogen research must be removed.

Progress in hallucinogen research in these areas has been slowed due to over-regulation. Given the endogenous nature of DMT, it deserves a special status for future research. It is evident that we have too long ignored the field of hallucinogen research, in all of its potential aspects. This is especially true if continuing research demonstrates a clear role for one of its more prominent members, DMT, as an endogenous regulator of brain function.

It is my opinion that these and many other possible approaches and hypotheses regarding DMT and other psychedelics are research endeavors that have great potential and are worthy of attention and support. Turning the newest technologies to this work, in genetics, analytical chemistry, molecular biology, imaging and others, we will no doubt acquire both new knowledge and ask new questions. If the politics of any one nation forbid it, perhaps others will take up the challenge to further the knowledge of our own potential and the further development and understanding of what we prize as our most unique human characteristic; the untapped possibilities of the mind.

The work presented is the sole effort of SB who agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. National Center for Biotechnology Information , U. Journal List Front Neurosci v.

Front Neurosci. Published online Aug 6. Steven A. Author information Article notes Copyright and License information Disclaimer. Barker ude.

This article was submitted to Neuropharmacology, a section of the journal Frontiers in Neuroscience. Received Oct 9; Accepted Jul The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these terms. This article has been cited by other articles in PMC. Abstract This report provides a historical overview of research concerning the endogenous hallucinogen N, N-dimethyltryptamine DMT , focusing on data regarding its biosynthesis and metabolism in the brain and peripheral tissues, methods and results for DMT detection in body fluids and brain, new sites of action for DMT, and new data regarding its possible physiological and therapeutic roles.

Keywords: N, N-dimethyltryptamine, hallucinogen, psychedelic, neurotransmitter, brain. Introduction Despite their presence in the human pharmacopeia for millennia, we have yet to resolve the biochemical mechanisms by which the hallucinogens psychedelics so dramatically alter perception and consciousness.

Open in a separate window. Figure 1. Figure 2. Future research on the biosynthesis of DMT Considering that tryptamine formation, itself a trace biogenic amine, is essential for the formation of DMT and given its own rapid metabolism by monoamine oxidase MAO as well, demonstrating its availability for the biosynthesis of DMT is also relevant to a complete elucidation of the overall pathway.

DMT metabolism The metabolism of DMT has been thoroughly studied, with a great deal of newer data being provided from studies of ayahuasca administration McIlhenny et al. Figure 3. DMT detection in blood, urine, and cerebrospinal fluid Barker et al. Future research to determine the concentration of DMT in brain tissues While more research into the brain concentrations and distribution of DMT is obviously warranted, it is possible, as with many other substances, that it may only be found in specific brain areas or cell types.

Imaging research While there have been several studies reporting neuroimaging data from volunteers consuming ayahuasca Bouso et al. Future imaging research The data to be derived in such imaging studies are highly dependent on the instrumentation and methods used and the interpretation of the data can often be somewhat subjective.

DMT as a neurotransmitter, neurohormone, or neuroregulatory substance In , Christian et al. Future studies characterizing DMT as a neurotransmitter Setting aside speculation in favor of what has been scientifically proven, the effects of administered psychedelics must be recognized as acting via existing, naturally occurring, neuropharmacological pathways and mechanisms. DMT as a therapeutic There has been a renewed interest in using hallucinogenic drugs as therapeutics in clinical research to address depression Berman et al.

Future study of DMT as a therapeutic At present, the data arguing for the use of DMT as a therapeutic, particularly via administration, is thin. Conclusions It has been 86 years since DMT's first synthesis by Manske and 61 years since Szara discovered its hallucinogenic properties. Author contributions The work presented is the sole effort of SB who agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Conflict of interest statement The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. References Aan het Rot M. Safety and efficacy of repeated dose intravenous ketamine for treatment-resistant depression. Psychiatry 67 , — Serotonergic psychedelics temporarily modify information transfer in humans. The hallucinogenic world of tryptamines: an updated review.

Enzymatic formation of psychotomimetic metabolites from normally occurring compounds. Science , — Tryptolines formation from tryptamines and 5-MTHF by human platelets. Comparison of the brain levels of N,N-dimethyltryptamine and alpha, alpha, beta, beta-tetradeutero-N,N-dimethyltryptamine following intraperitoneal injection.

A critical review of reports of endogenous psychedelic N,N-dimethyltryptamines in humans: — Drug Test. Metabolism of the hallucinogen N,N-dimethyltryptamine in rat brain homogenates. N,N-dimethyltryptamine: an endogenous hallucinogen. A comparison of the behavioral effects of proteo-and deutero-N,N-dimethyltryptamine.

Ontogeny of N,N-dimethyltryptamine and related indolealkylamine levels in neonatal rats. Ageing Dev. Inhibitory effect of 5-methoxy-N,N-dimethyltryptamine on the synaptosomal uptake of 5-hydroxytryptamine.

Antidepressant effects of ketamine in depressed patients. Psychiatry 47 , — The mode of action of 5-hydroxytryptamine. The nature of the binding between LSD and a 5-HT receptor: a possible explanation for hallucinogenic activity. Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes. Psychopharmacology , — Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.

Therapeutic mechanisms of classic hallucinogens in the treatment of addictions: from indirect evidence to testable hypotheses. Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans. Repeated lysergic acid diethylamide in an animal model of depression: normalization of learning behavior and hippocampal serotonin 5-HT2 signaling.

The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain. Dimethyltryptamine DMT : subjective effects and patterns of use among Australian recreational users. Drug Alcohol Depend. A proposed mechanism for the visions of dream sleep.

Hypotheses 26 , — Pharmacokinetics of Hoasca alkaloids in healthy humans. Neuropharmacology of N,N-dimethyltryptamine. Brain Res. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Serotonin and brain function: a tale of two receptors.

A half-century of neurotransmitter research: impact on neurology and psychiatry Nobel Lecture. Gas—liquid chromatographic separation and identification of biologically important indolealkylamines from human cerebrospinal fluid.

Evidence for dimethyltryptamine DMT as a naturally-occurring transmitter in mammalian brain. The in vitro identification of dimethyltryptamine DMT in mammalian brain and its characterization as a possible endogenous neuroregulatory agent. Sigma receptor modulators: a patent review. Expert Opin. Hallucinogenic N-methylated indolealkylamines in the cerebrospinal fluid of psychiatric control populations.

Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter. J Neural. Indolethylamine-N-methyltransferase expression in primate nervous tissue. Neuronal correlates of visual and auditory alertness in the DMT and ketamine model of psychosis.

A multidisciplinary overview of intoxicating enema rituals in the Western hemisphere. Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task. Neuroscience , — The current state of research on ayahuasca: a systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging.

Classical hallucinogens and neuroimaging: a systematic review of human studies. Hallucinogens and neuroimaging. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine. Oxidative N-dealkylation. Acta 18 , — A possible sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. A model for the application of target-controlled intravenous infusion for a prolonged immersive DMT psychedelic experience.

The psychedelic model of schizophrenia: the case of N,N-dimethyltryptamine. Psychiatry , — Serotonin receptor affinities of several hallucinogenic phenylalkylamine and N,N-dimethyltryptamine analogues. Biosynthesis of N,N-dimethyltryptamine DMT in a melanoma cell line and its metabolization by peroxidases. Ariquivos do Instituto de Pesquisas Agronomicas , 4 , 45— Hallucinogens recruit specific cortical 5-HT 2A receptor-mediated signaling pathways to affect behavior.

Neuron 53 , — On the transmethylation hypothesis: stress, N. Neuroprotective effects of the sigma-1 receptor ligand PRE- against excitotoxic perinatal brain injury in newborn mice. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Psychiatry 68 , 71— DPT as an adjunct in psychotherapy of alcoholics. Multiple receptors mediate the behavioral effects of indoleamine hallucinogens. Hallucinogen use predicts reduced recidivism among substance-involved offenders under community corrections supervision.

Blood and urine levels of N,N-dimethyltryptamine following administration of psychoactive dosages to human subjects. Psychopharmacologia 38 , — Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues.

Predicting new molecular targets for known drugs. Nature , — The sigma-1 receptor: roles in neuronal plasticity and disease. Trends Neurosci.

Dreams and psychedelics: neurophenomenological comparison and therapeutic implications. Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation. Lysergic acid diethylamide LSD for alcoholism: meta-analysis of randomized controlled trials. Evidence for the absence of amine-N-methylation and O-methylation in indolethylamines with methyltetrahydrofolic acid-dependent N-methyltransferase.

Indolethylamine-N-methyltransferase in developing rabbit lung. Pharmacologist 16 Treatment of alcoholism using psychedelic drugs: a review of the program of research. Psychoactive Drugs 30 , — A synthesis of the methyltryptamines and some derivatives. Development of the sigma-1 receptor in C-terminals of motoneurons and colocalization with the N, N- dimethyltryptamine forming enzyme, indole-N-methyl transferase. Neuroscience , 60— Methodology for determining major constituents of ayahuasca and their metabolites in blood.

Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. The scientific investigation of ayahuasca: a review of past and current research.

Heffter Rev. Psychedelic Res. Differential interactions of indolealkylamines with 5-hydroxytryptamine receptor subtypes. Neuropharmacology 29 , — Cardena, M.

Winkleman Oxford: Praeger Press; , 85— Effects of iproniazid, chlorpromazine and methiothepin on DMT-induced changes in body temperature, pupillary dilatation, blood pressure and EEG in the rabbit.

Hallucinogen-induced relief of obsessions and compulsions. Indole ethyl amine N-methyltransferase in the brain. The effects of non- medically used psychoactive drugs on monoamine neurotransmission in rat brain.

Inhibitor of indolethylatimine-N-methyltransferase in pineal extract. Structure—activity relationships of serotonin 5-HT2A agonists. WIREs Membr. N,N-dimethyltryptamine and the pineal gland: separating fact from myth. Cystathionine b-synthase deficiency causes infertility by impairing decidualization and gene expression networks in uterus implantation sites.

Genomics 44 , — The EGR family of transcription-regulatory factors: progress at the interface of molecular and systems neuroscience. Schizophrenia: a new approach. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report.

Pharmahuasca: human pharmacology of oral DMT plus harmine. Drugs 31 , — Behavioural and neurotoxic effects of ayahuasca infusion Banisteriopsis caapi and Psychotria viridis in female Wistar rat. Quantitative assay of the N-methylated metabolites of tryptamine and serotonin by gas chromatography mass spectrometry as applied to the determination of lung indole-ethylamine N-methyltransferase activity.

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