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The present disclosure relates in some aspects to methods for modulating and improving the subjective experience of N,N-dimethyltryptamine (DMT) by administering DMT after a long-acting tryptamine such as psilacetin, 

https://rentry.co/itzekhjshsgvshsgsjjjshsggsvv in some embodiments, together with a benzodiazepine and/or ketamine, or in some further embodiments, together with a second long-acting psychedelic. 

https://rentry.co/itzekhjshsgvshsgsjjjshsggsvv In some aspects, disclosed methods are useful for treating medical conditions, such as mental health disorders and neurodegenerative disorders. In some aspects, disclosed methods are useful for improving health and wellbeing, such as in healthy people.Psychedelics” refers to a class of drugs which elicit certain cognitive, emotional, perceptual, physiological, psychological, and other effects. These effects may result in an altered or “non-ordinary” state of consciousness, which can include vivid visual and auditory perceptual changes, often accompanied by intense emotional, mystical, or “spiritual” experiences.

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a dr#g that can be combined with mixing agents to produce an E-liquid pen cartridge DMT pens allow users more consistent control over dosage and hallucinogenic effectsThere is little to no data regarding the safety or potential health risks of an experience with DMT pens Drinking ayahuasca brewed from banisteriopsis caapi or smoking powder from a glass pipe isn’t the only way to have a psychedelic experience with the psychedelic drug DMT, also called the “spirit molecule”. It can also be mixed into E-liquid, casually referred to as “cart juice” with propylene glycol and vitamin E acetate, and inhaled using common vaporizers or E-cigarettes as DMT pens.

What DMT pen/mods do I need to use this with?Any mod will do really. It just needs to be able to output a low enough power so that it doesn't fry the carts atomizer.Carts are meant for pen batteries but box mods can work fine, you just have to be careful not to give the cart to much power.Something can change the wattage or voltage in small increments is better for carts. Like 0.1 watt increments carts and get the experience you expect.

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Dimethyltryptamine (DMT) is a naturally 5meo dmt for sale hallucinogenic tryptamine substance that has been utilized for generations in religious shaman ceremonies and rituals. It's also called as the "spirit molecule" because of its powerful psychedelic effects, which can include altered perception of space and time while taking you on a "businessman's trip."

DMT is a naturally occurring hallucinogenic substance found in plants such as Acacia bark, among others. because when smoked during aya, aided by hallucinations so powerful that they believed these otherworldly entities lived outside of themselves

Psychedelic effects include effects on the mind, effects on mood, and visual effects. The duration of psychedelic effects experienced by an individual after consuming a psychedelic substance can vary depending on the type of substance, dose, as well as the genetic and physiological disposition of the subject.

“Long-acting psychedelics” refers in some embodiments to psychedelics with a duration of effects of at least 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, or 12 hours. Measures of duration of effects may be known by reference to general knowledge in the art, or where not known in the art, may be determined by methods known by those of ordinary skill. For example, the duration of effects from a known dose of a known substance may be proportional to its elimination half life. In some embodiments, a “long-acting psychedelic” has an elimination half-life of at least 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, or 6 hours.

In some embodiments, the long-acting psychedelic has a duration of effects of between 1 and 4 hours. In some embodiments, the long-acting psychedelic is any of DPT, EPT, 4-AcO-DiPT, and 4-HO-DiPT.

In some embodiments, the long-acting psychedelic has a duration of effects of between 4 and 8 hours. In some embodiments, the long-acting psychedelic is any of psilocybin, ayahuasca, 1cP-MiPLA, LAE-32, MiPLA, PARGY-LAD, PRO-LAD, DET, DiPT, MiPT, 4-AcO-DET, 4-AcO-DMT (psilacetin), 4-AcO-MET, 4-AcO-MiPT, 4-HO-DET, 4-HO-DPT, 4-HO-EPT, 4-HO-MET, 4-HO-MiPT, 4-HO-MPT, 5-MeO-DALT, 5-MeO-DiPT, 5-MeO-MiPT, 4-HO-DMT (psilocin), 2C-B, 2C-C, 2C-D, 2C-T, 2, 5-DMA, and 2C-D.

In some embodiments, the long-acting psychedelic has a duration of effects of between 8 and 12 hours. In some embodiments, the long-acting psychedelic is any of LSD, 1B-LSD, mescaline, 1cP-AL-LAD, 1cP-LSD, 1P-ETH-LAD, 1P-LSD, 1V-LSD, AL-LAD, ALD-52 (1A-LSD), ETH-LAD, LSA, LSM-775, LSZ, allylescaline, escaline, mescaline, methallylescaline, proscaline, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21, 2C-B-FLY, Bk-2C-B, B-MeO-2C-D (BOD), TMA-2, and TMA.

In some embodiments, the long-acting psychedelic has a duration of effects of greater than 12 hours. In some embodiments, the long-acting psychedelic is any of AMT, 5-MeO-aMT, ibogaine, 3C-E, 3C-P, 2C-P, DOB, DOC, DOI, DOM, and TMA-6.

In some embodiments, the long-acting psychedelic is a tryptamine. “Tryptamines” are as readily understood by those in the art, and include for example any substituted tryptamine having the structure below, wherein RN1, RN2, Rα, Rβ, R2, R4, R5, R6, and R7 are as taught herein and as generally understood in the art:

Figure US12396981-20250826-C00001

For example, in some embodiments, RN1, RN2, Rα, Rβ, R2, R4, R5, R6, and R7 are independently hydrogen, deuterium, halogen, hydroxy, methoxy, phosphoryloxy, C1-C5 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closed with the nitrogen), C3-C8 cycloalkenyl (independently or ring closed with the nitrogen), aryl, or heterocyclyl, any of which are optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate, —OP(O)(OH)2, —OC(O)H, —OSO2OH, —OC(O)NH2, and —SONH. In some embodiments, such tryptamines are useful in the practice of disclosed methods, and include tryptamines which are long-acting psychedelics according to embodiments herein.

Other non-limiting examples of tryptamines, useful in the practice of disclosed methods, and including tryptamines which are long-acting psychedelics according to embodiments herein, include as examples N,N-dibutyltryptamine (DBT), N,N-diethyltryptamine (DET), N,N-diisopropyltryptamine (DiPT), 5-methoxy-α-methyltryptamine (α,O-DMS), 2,α-dimethyltryptamine (2,α-DMT), α,N-dimethyltryptamine (α,N-DMT), N,N-dipropyltryptamine (DPT), N-ethyl-N-isopropyltryptamine (EiPT), α-ethyltryptamine (AET), 3,4-dihydro-7-methoxy-1-methylcarboline (Harmaline), 7-methoxy-1-methylcarboline (Harmine), N,N-dibutyl-4-hydroxytryptamine (4-HO-DBT), N,N-diethyl-4-hydroxytryptamine (4-HO-DET), N,N-diisopropyl-4-hydroxytryptamine (4-HO-DiPT), N,N-dimethyl-4-hydroxytryptamine (4-HO-DMT), N,N-dipropyl-4-hydroxytryptamine (4-HO-DPT), N-ethyl-4-hydroxy-N-methyltryptamine (4-HO-MET), 4-hydroxy-N-isopropyl-N-methyltryptamine (4-HO-MiPT), 4-hydroxy-N-methyl-N-propyl-tryptamine (4-HO-MPT), 4-hydroxy-N,N-tetramethylenetryptamine (4-HO-pyr-T), 12-methoxyibogamine (Ibogaine), N-butyl-N-methyltryptamine (MBT), N,N-diisopropyl-4,5-methylenedioxytryptamine (4,5-MDO-DiPT), N,N-diisopropyl-5,6-methylenedioxytryptamine (5,6-MDO-DiPT), N,N-dimethyl-4,5-methylenedioxytryptamine (4,5-MDO-DMT), N,N-dimethyl-5,6-methylenedioxytryptamine (5,6-MDO-DMT), N-isopropyl-N-methyl-5,6-methylenedioxytryptamine (5,6-MDO-MiPT), N,N-diethyl-2-methyltryptamine (2-Me-DET), 2,N,N-trimethyltryptamine (2-Me-DMT), N-acetyl-5-methoxytryptamine (melatonin), N,N-diethyl-5-methoxytryptamine (5-MeO-DET), N,N-diisopropyl-5-methoxytryptamine (5-MeO-DiPT), N-isopropyl-4-methoxy-N-methyltryptamine (4-MeO-MiPT), N-isopropyl-5-methoxy-N-methyltryptamine (5-MeO-MiPT), 5,6-dimethoxy-N-isopropyl-N-methyltryptamine (5,6-MeO-MiPT), 5-methoxy-N-methyl-tryptamine (5-MeO-NMT), 5-methoxy-N,N-tetramethylenetryptamine (5-MeO-pyr-T), 6-methoxy-1-methyl-1,2,3,4-tetrahydrocarboline (6-MeO-THH), 5-methoxy-2,N,N-trimethyl-tryptamine (5-MeO-TMT), N,N-dimethyl-5-methylthiotryptamine (5-MeS-DMT), N-isopropyl-N-methyltryptamine (MiPT), α-methyltryptamine (α-MT), N-ethyltryptamine (NET), N-methyltryptamine (NMT), N,N-tetramethylenetryptamine (pyr-T), Tryptamine (T), 7-methoxy-1-methyl-1,2,3,4-tetrahydrocarboline (Tetrahydroharmine), and α,N-dimethyl-5-methoxytryptamine (α,N,O-TMS), as well as any pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, analog, derivative, metabolite, variant, or isotopolog thereof, and combination of any of the foregoing thereof. See, e.g., Shulgin & Shulgin, TiHKAL: The Continuation, Transform Press (1997) (“TiHKAL”), which is incorporated by reference as if fully set forth herein.some embodiments, the long-acting psychedelic is selected from the group consisting of:

4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT; psilocin),

4-phosphoryloxy-N,N-dimethyltryptamine (4-OPO3H2-DMT; psilocybin),

4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT; psilacetin),

N,N-diethyltryptamine (DET),

4-hydroxy-N,N-diethyltryptamine (4-HO-DET),

4-phosphoryloxy-N,N-diethyltryptamine (4-OPO3H2-DET),

4-acetoxy-N,N-diethyltryptamine (4-AcO-DET),

N,N-diisopropyltryptamine (DiPT),

4-hydroxy-N,N-diisopropyltryptamine (4-HO-DiPT),

4-phosphoryloxy-N,N-diisopropyltryptamine (4-OPO3H2-DiPT),

4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DiPT),

5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT),

N,N-dipropyltryptamine (DPT),

4-hydroxy-N,N-dipropyltryptamine (4-HO-DPT),

4-phosphoryloxy-N,N-dipropyltryptamine (4-OPO3H2-DPT),

4-acetoxy-N,N-dipropyltryptamine (4-AcO-DPT),

N,N-dibutyltryptamine (DBT),

4-hydroxy-N,N-dibutyltryptamine (4-HO-DBT),

4-phosphoryloxy-N,N-dibutyltryptamine (4-OPO3H2-DBT),

4-acetoxy-N,N-dibutyltryptamine (4-AcO-DBT),

4-hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET),

4-phosphoryloxy-N-methyl-N-ethyltryptamine (4-OPO3H2-MET),

4-acetoxy-N-methyl-N-ethyltryptamine (4-AcO-MET),

N-methyl-N-isopropyltryptamine (MiPT),

4-hydroxy-N-methyl-N-isopropyltryptamine (4-HO-MiPT),

4-phosphoryloxy-N-methyl-N-isopropyltryptamine (4-OPO3H2-MiPT),

4-acetoxy-N-methyl-N-isopropyltryptamine (4-AcO-MiPT),

5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT),

4-hydroxy-N-methyl-N-propyltryptamine (4-HO-MPT),

4-phosphoryloxy-N-methyl-N-propyltryptamine (4-OPO3H2-MPT),

4-acetoxy-N-methyl-N-propyltryptamine (4-AcO-MPT),

5-methoxy-4-hydroxy-N,N-dimethyltryptamine (psilomethoxin), and

5-methoxy-N,N-diallyltryptamine (5-MeO-DALT);

and pharmaceutically acceptable salts thereof.

In some embodiments, the long-acting tryptamine is a 4-substituted tryptamine. In some embodiments, the 4-substituted tryptamine is a 4-hydroxytryptamine (e.g., psilocin). In some embodiments, the 4-substituted tryptamine is a 4-phosphoryloxytryptamine (e.g., psilocybin). In some embodiments, the 4-substituted tryptamine is a 4-acetoxytryptamine (e.g., psilacetin). In some embodiments, the 4-substituted tryptamine is psilocin or psilocybin, or a pharmaceutically acceptable salt thereof. In some embodiments, the 4-substituted tryptamine is psilocin, psilocybin, or psilacetin, or a pharmaceutically acceptable salt thereof.

In some embodiments, the long-acting tryptamine is a 4-substituted tryptamine selected from the group consisting of:

4-hydroxy-N,N-dimethyltryptamine (4-OH, DMT; psilocin),

4-phosphoryloxy-N,N-dimethyltryptamine (4-OPO3H2-DMT; psilocybin),

4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT; psilacetin),

4-hydroxy-N,N-diethyltryptamine (4-HO-DET),

4-phosphoryloxy-N,N-diethyltryptamine (4-OPO3H2-DET),

4-acetoxy-N,N-diethyltryptamine (4-AcO-DET),

4-hydroxy-N,N-diisopropyltryptamine (4-HO-DiPT),

4-phosphoryloxy-N,N-diisopropyltryptamine (4-OPO3H2-DiPT),

4-acetoxy-N,N-diisopropyltryptamine (4-AcO-DiPT),

4-hydroxy-N,N-dipropyltryptamine (4-HO-DPT),

4-phosphoryloxy-N,N-dipropyltryptamine (4-OPO3H2-DPT),

4-acetoxy-N,N-dipropyltryptamine (4-AcO-DPT),

4-hydroxy-N,N-dibutyltryptamine (4-HO-DBT),

4-phosphoryloxy-N,N-dibutyltryptamine (4-OPO3H2-DBT),

4-acetoxy-N,N-dibutyltryptamine (4-AcO-DBT),

4-hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET),

4-phosphoryloxy-N-methyl-N-ethyltryptamine (4-OPO3H2-MET),

4-acetoxy-N-methyl-N-ethyltryptamine (4-AcO-MET),

4-hydroxy-N-methyl-N-isopropyltryptamine (4-HO-MiPT),

4-phosphoryloxy-N-methyl-N-isopropyltryptamine (4-OPO3H2-MiPT),

4-acetoxy-N-methyl-N-isopropyltryptamine (4-AcO-MiPT),

4-hydroxy-N-methyl-N-propyltryptamine (4-HO-MPT),

4-phosphoryloxy-N-methyl-N-propyltryptamine (4-OPO3H2-MPT), and

4-acetoxy-N-methyl-N-propyltryptamine (4-AcO-MPT);

and pharmaceutically acceptable salts thereof.Example 4: Assessing Synergistic Effects of Disclosed Combinations and Methods

Synergistic effects of disclosed combinations and methods are assessed in a clinical study in which DMT, a long-acting psychedelic, a benzodiazepine, and ketamine are administered to different participant groups in the following combinations:

Group 1 Group 2 Group 3 Group 4 Group 5

Drug(s) DMT DMT DMT DMT DMT

Long-acting Long-acting Long-acting Long-acting

tryptamine tryptamine tryptamine tryptamine

Benzodiazepine Ketamine Benzodiazepine

Ketamine

The doses of DMT used in each study are equivalent for the purposes of comparison. After inhaling DMT, synergistic effects of disclosed combinations are assessed by administered a questionnaire to participants in each group, such as the Mystical Experience Questionnaire (MEQ30), the Challenging Experience Questionnaire (CEQ), or the Hallucinogen Rating Scale (HRS), the Mysticism Scale (M-scale) or Hood Mysticism Scale (HMS), the Five Dimensional or 11-Dimensional Altered States of Consciousness Questionnaire (5D-ASC or 11D-ASC), the States of Consciousness Questionnaire (SOCQ), the Ego Dissolution Inventory (EDI), or the Phenomenology of Consciousness Inventory (PCI).

Assessing synergistic effects can also include obtaining objective health measurements from the patient, (herein, “objective measurements,”) including but not limited to weight, body temperature, heart rate (HR), respiratory rate, blood oxygenation, blood pressure (BP) and its variables, including, but not limited to: systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP); continuous non-invasive beat-by-beat blood pressure (CNIBP); measurements from an electrocardiogram (ECG), including RR interval or its variability, QT interval or its variability, heart rate variability (HRV) (or measured by devices other than an ECG); hemodynamic response (HR), and levels of glucose, cortisol, serotonin, dopamine, cholesterol; electroencephalography (EEG) measures such as quantitative EEG (qEEG); electrocochleogram (ECochG), electromyography (EMG), electrooculography (EOG), magnetoencephalography (MEG); electrocorticography (ECoG); magnetic resonance imaging (MRI); functional MRI (fMRI); computed tomography (CT); positron emission tomography (PET); nuclear magnetic resonance (NMR) spectroscopy or magnetic resonance spectroscopy (MSR); single-photon emission computed tomography (SPECT); near infrared spectroscopy (NIRS); event-related optical signal (EROS); computed axial tomography; diffuse optical imaging (DOI); cranial ultrasound; or functional ultrasound imaging (fUS) (together, “EEG measures”).

Synergistic effects may also result from changes in drug metabolism, which can manifest through altered pharmacokinetics and altered elimination rates. Such factors, and others indicative of potentially synergistic drug-drug interactions, can be measured according to standard techniques, for instance HPLC analysis of metabolite profiles in serum, plasma, blood, or urine.

Results may show that administering DMT according to a disclosed method (e.g., in combination with a long-acting tryptamine, and optionally further in combination with a benzodiazepine, ketamine, and any additional active agents) results in synergistic effects. Such synergistic effects may improve the subjective DMT experience, as well as manifest as advantageous pharmacokinetic and/or pharmacodynamic properties, as described in embodiments herein.

Example 5: Natural Language Processing to Assess Improvements to the DMT Experience

A study is conducted to compare the experience of inhaled DMT alone with the effects of a inhaled DMT according to a disclosed method. Subjects will be divided into four treatment groups; (1) DMT administered alone, (2) DMT administered with a long-acting psychedelic, (3) DMT administered with a long-acting psychedelic and a benzodiazepine, and (4) DMT administered with a long-acting psychedelic, a benzodiazepine, and an NMDAR antagonist.