Administration ofN,N- dimethyltryptamine [ DMT] vapes how it works and where to buy

[Bayscare Silicone]

Administration of DMT
Administration of DMT
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
Ayahuasca as a source of DMT in psychedelic therapeutics
There has already been a significant and historical record for the medicinal use of DMT occurring long before the advent of psychedelic therapy. Like many foundational therapeutics, N,N-dimethyltryptamine (DMT) literally has botanical roots and an archaic cultural history of use for medicine and religious ritual, much as does psilocybin. As a psychoactive ethnobotanical medicine utilized by many of the indigenous tribes of the Basin of South America, the DMT-containing tisanes or teas known collectively as yage, caapi, hoasca, or ayahuasca have been in use for hundreds of years in these cultures (Samorini 2019). Ayahuasca, a Quechua tribal term meaning ‘‘vine of the souls,’’ is used in the context of shamanistic ritual, as historically practiced among aboriginal peoples for curing, divination, diagnosis of the imbalances of the body and soul, and as a ready pharmacological path to the mythological supernatural.

The major active component, DMT, comes from the leaves of the Psychotria species, mainly P. viridis. Since the major metabolic route for DMT in humans involves conversion to indol-3-acetic acid by MAO (Barker et al., 1981), teas made from Psychotria species alone are not orally active, but when combined with the harmala MAOIs (harmine, harmaline) of Banisteriopsis caapi, it becomes a potent hallucinogenic beverage (Schultes, 1957; McKenna et al. 1984, 1998; Andritzky, 1989).
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/

The effects of consuming ayahuasca have been variously summarized as “… inducing changes in the perceptual, affective, cognitive, and somatic spheres, with a combination of stimulatory and visual psychoactive effects of longer duration and milder intensity than those previously reported for intravenously administered DMT.” (Riba et al. 2001; Riba 2003). Pharmacological studies of acute ayahuasca administration to healthy volunteers and mental health assessments of long-term ayahuasca consumers suggest that this ethnobotanical medicine is relatively safe and effective (Callaway et al. 1999; dos Santos, et al. 2011, 2016a, 2016b, 2017). However, questions remain about the ability to provide a consistent “batch” of ayahuasca for further study and therapeutic use on a larger scale.

One of several difficulties that has arisen for the use of ayahuasca as a clinical therapeutic involves its uniformity and stability. A recent study of the main ayahuasca alkaloids (DMT, harmine, tetrahydroharmine, and harmaline) in brewed ayahuasca stored under three different conditions (1 year stored in a refrigerator either in plastic or glass containers, 7 days at 37 °C and after three freeze–thaw cycles) found that there was no significant degradation of DMT concentration over time in all tested environments. However, the harmala alkaloids all showed significant degradation under long-term storage and at elevated temperature as well as possible alkaloid inter-conversion. It was concluded by the authors that ayahuasca tea component quantification before administration under controlled conditions would be mandatory (Silveira et al. 2020). Similarly, batch-to-batch ayahuasca preparation variation as well as alterations in ayahuasca alkaloid content as a function of season, location, soil, and climate conditions, and other variables related to plant growth, have been consistently observed, leading to wide-ranging dosing levels, and making adjustment of ayahuasca by dilution or addition of components necessary to obtain a relatively consistent material for use. The use of large batch, freeze-dried material administered in a gelatin capsule can overcome some of these issues (Riba and Barbanoj 2005), but not all. Therapeutic use of ayahuasca suggests that it can have prolonged antidepressant, anxiolytic, and anti-addictive effects (dos Santos et al. 2016a, 2016b), and is also quite safe (dos Santos et al. 2016a, 2016b; Osório et al. 2015; Frecska et al., 2016).

To understand the potential of ayahuasca to contribute to modern medicine and its use in psychedelic therapeutics, it must be more thoroughly examined in the laboratory and in controlled clinical trials and medicinal studies (Kuypers et al., 2016; Palhano-Fontes et al., 2019). Nonetheless, an approach to its therapeutic use has been outlined and described (McKenna 2004). While ayahuasca obviously holds promise in many social, cultural, and therapeutic paradigms, including treatment of addiction, anxiety, and depression in psychiatry and many other possible applications, it is, nonetheless, a complex mixture of perhaps thousands of compounds. A further complication in its use in therapeutics and research is that the potent MAOI activity of the harmala alkaloids not only protects DMT from metabolic degradation but also suppresses the metabolism of other neurotransmitters and MAO-sensitive compounds in the brain and periphery. These compounds also have their own unique pharmacology. Thus, it is difficult to know exactly which of the compounds or combination of compounds plays a role in what observed effect (Ona et al., 2020), making it difficult to compare to studies conducted using DMT alone.

2. Administration of DMT with and without a MAOI: doses, routes, and effects
Oral administration of DMT alone is rendered neurochemically inactive by MAO during first-pass metabolism. Thus, other routes for the administration of DMT have been designed to avoid or mitigate this fate. These have predominantly required intravenous (IV) or intramuscular (IM) administration, inhalation (smoking or sublimation) or insufflation (nasal sprays, snuffs), and use of transdermal, sublingual, or buccal absorption. Other routes have been attempted with little reported success. It is of interest to note that intranasal free-base DMT is inactive (0.07–0.28 mg/kg; Turner and Merlis 1959) as is DMT administered rectally (De Smet 1983).

Szára (1956, 1961) reported that the effects of intramuscular DMT (0.7 mg/kg) were like mescaline and LSD (visual illusions and hallucinations, distortion of body image, speech disturbances, mood changes, and euphoria or anxiety). Other studies using either IV or IM administrations (Turner and Merlis 1959; Rosenberg et al. 1964; Gillin et al. 1976; Strassman et al. 1994a, 1994b) have observed similar results. The intramuscular effects of DMT (0.2–1 mg/kg; Szára 2007) generally had a rapid onset (2–5 min) and lasted 30–60 min. The IM effects were considered less intense than the IV route. As a comparison, the subjective effects of DMT from ayahuasca administration (0.6–0.85 mg/kg DMT; Riba et al. 2003) usually appear within 60 min, peak at 90 min, and can last for approximately 4 h (Cakic et al. 2010), due, in part, to the MAOI effects of the constituent harmala alkaloids. Riba et al. (2015) have reported the comparative effects of oral and vaporized DMT. Oral ingestion of pure DMT produced no psychotropic effects, as expected. Vaporized DMT was found to be a highly psychoactive route of administration, however. Doses for vaporized or inhaled free-base DMT are typically 40–50 mg, although larger doses have been reported (100 mg; Shulgin and Shulgin 1997). Pallavicini et al. (2021) have reported that vaporization of approximately 40 mg of DMT, administered in a natural setting, produced potential electroencephalographic markers of mystical-type experiences in 35 volunteers. The onset of effects for inhaled DMT is rapid, similar to that of IV administration, but lasts less than 30 min (Riba et al. 2015; Davis et al. 2020). However, smoked, vaporized, or insufflated DMT can often be harsh and is not always well-tolerated. Thus, these routes may not be the most consistent and suitable choices for therapy.

Strassman et al. (1994a, 1994b) have reported dose–response data for intravenously administered DMT fumarate in a group of experienced hallucinogen users (n = 11). DMT was administered IV at doses of 0.05, 0.1, 0.2, and 0.4 mg/kg and showed peak DMT blood levels and subjective effects within 2 min after drug administration, becoming negligible at 30 min. IV DMT was also shown to elevate blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of β-endorphin, corticotropin, and cortisol in a dose-dependent manner, with prolactin and growth hormone levels rising equally, regardless of dose. The lowest dose that produced statistically significant effects relative to placebo and that was also hallucinogenic was 0.2 mg/kg (Strassman 1991, 1996, 2001; Strassman et al. 1996). For exogenously administered DMT, we know plasma concentrations between 12 and 90 ng/ml (Callaway et al. 1999; Yritia et al. 2002; Riba et al. 2003) must be attained to produce hallucinogenic effects. However, the concentrations attained in whole brain or in specific brain cells or areas that are required to produce hallucinogenic effects from such administrations in humans remains unknown.

The use of a simple mixture of DMT and harmaline and/or harmine or other MAOIs, a so-called “pharmahuasca” (Ott 1999; Brierley and Davidson 2012), has been proposed as a “cleaner,” orally administered substitute for ayahuasca itself or of greater use in conducting ayahuasca research as a pharmaceutical version of the entheogenic brew. For administration of pharmahuasca, 50 mg DMT:100 mg harmaline is usually the recommended dosage. However, combinations of 50 mg harmaline:50 mg harmine and 50 mg DMT have been tested with success. The harmalas and DMT are typically put into separate gelatin capsules, with the harmaline/harmine being taken first and the DMT being taken 15 to 20 min later. The use of moclobemide, a reversible inhibitor of MAO-A, has also been reported in DMT “pharmahuasca” studies (Kaasik et al. 2020; Ruffell et al. 2020).

The further study of “pharmahuasca,” as well as more research on low-dose ayahuasca, may prove to be rewarding for their use as psychedelic therapeutics. However, as with ayahuasca, the concomitant use of an MAOI remains a drawback.
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/

3. Micro-dosing or low-dosing of non-hallucinogenic amounts of DMT
More recently, data and anecdotal reports concerning the physiological effects of administration of psychedelics in very low doses, or micro-dosing, have gained significant public attention. Micro-dosing of psychedelics refers to the ingestion of low to very low doses (5 and 10% of a standard hallucinogenic dose) on an established schedule (every other day) with the intention of avoiding hallucinogenic or short-term debilitating effects (Fadiman and Korb, 2019; Kuypers et al. 2019; Kuypers, 2020; Liechti 2019, Bershad et al. 2019 Cameron et al. 2020). However, regardless of the identity of the psychedelic, there are no scientifically established dose ranges that have been accepted for micro-doses of these substances (Kuypers et al. 2019; Passie 2019; Lea et al. 2020). In its popular practice, micro-dosing is said to enhance productivity, focus, and creative problem solving (Dean 2017; Glatter 2015; Cameron et al. 2020) and as a self-regulated treatment for depression, anxiety, and other perceived mental disorders (Waldman 2017; Hutten et al. 2019). Recent randomized controlled trials, mainly with LSD or psilocybin, have reported changes in time perception (LSD; Yanakieva et al. 2019), dose-related increases in ratings of “vigor” (psilocybin; Bershad et al. 2019), and improved performance on problem-solving tasks (psilocybin mushrooms; Prochazkova et al. 2018). However, the number of such studies is currently too small to draw any scientifically significant conclusions.

Similarly, there are but a handful of such DMT micro- or low-dosing studies, conducted in species other than humans (predominantly the rat), published in the scientific literature. However, the translational aspect of a low dose in rats and a micro-dose in a human is not yet established and no scientifically sound conclusions can yet be drawn. Nonetheless, Ly et al. (2018) observed that a low dose of DMT caused changes in the frequency and amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in the prefrontal cortex (PFC) of rats that lasted long after the drug had been cleared from the body. Cameron et al. (2019) examined these observations further by subjecting male and female Sprague–Dawley (SD) rats to behavioral testing following the chronic, intermittent administration of low doses of DMT (approximately for 2 months, every third day, 1 mg/kg, IP). The behavioral and cellular effects observed were distinct from those induced following a single high dose of DMT (10 mg/kg IP), producing an antidepressant-like phenotype and enhanced fear-extinction-learning without impacting working memory or social interaction. At this low dose, DMT showed a distinct lack of anxiogenic effects, a striking difference between low dose and a single high dose of DMT, which is known to produce intense initial anxiogenic effects in several animal behavioral tests and in humans. A similar phenomenon was observed by Strassman et al. (1994b) wherein a single 0.1 mg/kg dose of DMT administered IV to humans, which was sub-hallucinogenic, produced an apparent anxiolytic effect.
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/

Tested in rats in other behavioral paradigms (foot shock; cued fear learning) low-dose DMT showed no difference from placebo, whereas a single high dose of DMT significantly increased freezing levels immediately following foot shocks (Cameron et al. 2019). When the cued memory test was repeated, the low-dose DMT-treated animals froze significantly less than the vehicle controls (p = 0.03), suggesting that chronic, intermittent, low doses of DMT facilitate fear-extinction learning. In the forced swim behavioral test, however, both low-dose intermittent DMT and single high-dose DMT elicited an antidepressant-like effect, consistent with anecdotal reports from human use. Chronic, intermittent, low doses of DMT had no effect on working/short-term memory or social interaction, seemingly in contradiction to the beneficial effects of psychedelic micro-dosing reported by humans (Cameron et al. 2019).

A previous study had shown that a single intraperitoneal (IP) high dose of DMT (10 mg/kg IP) in rats increases dendritic spine density in the prefrontal cortex (Cameron et al. 2018). However, Cameron et al. (2019) showed no such effect from low-dose intermittent IP administration of DMT in male SD rats. Rather, they reported a significant decrease in dendritic spine density in females under these conditions when compared to placebo controls (p = 0.03). The expression of several key prefrontal cortex genes (egr1, egr2, arc, and fos) associated with neuronal plasticity was also examined following low-dose intermittent administration, as acute doses of psychedelics are known to increase their expression (Martin and Nichols 2017). However, low doses of DMT did not alter the expression of any of these genes nor did it increase the expression of BDNF, which is increased in rat cortex following both acute (Vaidya et al., 1997; administration of DOI: 4-iodo-2,5-dimethoxyphenylisopropylamine) and chronic administration (Martin et al. 2014: administration of LSD) of high doses of psychedelics. An interesting finding was that 5HT2A receptor gene expression was unchanged despite chronic exposure of the 5HT2A receptor to DMT for nearly 2 months. These data suggest that psychedelic micro- or low dosing with DMT may be effective in treating symptoms of mood and anxiety disorders, though much further investigation is clearly required. However, they also suggest the possibility that two pharmacologies are at work: one for high dose and one for low dose. The work of Cameron et al. (2018, 2019) is thus informative in this regard and, perhaps, a warning for those who choose micro-dose or low-dose experimentation without first knowing the data or before scientifically controlled research and safety studies have been conducted.

How do we best administer therapeutic or research doses of DMT?
While the use of a pharmahuasca formulation could serve to standardize ayahuasca administrations, lower the dose needed to obtain desired outcomes, avoid many side effects observed from the use of ayahuasca itself, and provide a convenient oral route for its use as a therapeutic; it suffers from one of the same problems as ayahuasca—the n
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/

https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
https://southparkpsychedelics.com/product-category/dmt-vapes-and-cartriges/
How do we best administer therapeutic or research doses of DMT?
While the use of a pharmahuasca formulation could serve to standardize ayahuasca administrations, lower the dose needed to obtain desired outcomes, avoid many side effects observed from the use of ayahuasca itself, and provide a convenient oral route for its use as a therapeutic; it suffers from one of the same problems as ayahuasca—the necessary, general, system-wide inhibition of MAO, producing a mixed pharmacology that will be difficult to scientifically untangle even while simplifying some therapeutic applications.

Indeed, there seems to be no ideal or “conveniently unobtrusive” route for routine administration of DMT for general or common therapeutic use, although this may depend on whether an acute or prolonged dosing regimen is required. Any administration route using IV or IM routes, or inhalation or insufflation will be useful for conducting acute exposures where prescribed and rendered tolerable. One may assume that formulations for possible dosing by sublingual or buccal administrations could be developed that overcome their individual issues and difficulties (taste, salivary clearance, adsorption rates) while avoiding first-pass metabolism. New developments in “patch” dermal delivery systems as well as drug delivery “pumps” may also be applicable for time-release DMT administration. Metered dosing of an aerosolized solution of DMT using an inhaler-type device has also been suggested (Arnold et al. 2021) and “vaping” is already a popular, though anecdotal, route of use. However, a simple orally administered pill is often the most desirable for pharmaceutical use for most therapeutics, especially if repeated dosing and longer term therapy is found to be successful. The pill need not be simple, however. Newer technology in delayed release, sustained release, and complex excipient combinations may also prove to have their place for DMT as well as other psychedelic therapies for routine low- or high-level dosing.

The need to provide an orally administered DMT that resists metabolism, without necessitating an add-on MAOI, that still retains potency and efficacy for a desired treatment, for which it may eventually be deemed appropriate, can be accomplished by slight modifications of the structure of the DMT molecule. These modifications mainly involve altering the ability of MAO to bind and cleave the DMT molecule at the side chain carbon-alpha to the nitrogen, which is the mechanism of action of MAO (Vianello et al. 2012) in the process of converting ethylamine indolic side chains to the corresponding indole acetic acid.

Another approach commonly used in medicinal chemistry is to change the dimethyl groups on the side chain nitrogen to larger and/or branched alkyl substituents to again limit the ability of MAO to bind and metabolize the molecule. A combination of both may prove successful as well. Literally locking the side chain into a ring, as is seen in lysergic acid dimethylamide (LSD), also has its advantages. The complicating factors in these modifications may be that, while they inhibit DMT’s metabolism and clearance, such alterations may cause them to fail to properly bind, altering the binding characteristics at, for example, the 5HT2a receptor, or may produce an overall differing pharmacology or toxicology. They could also prove to be more effective.

However, two studies have shown that alteration of the alpha and beta hydrogens on the side chain of DMT and its structural relative, 5MeODMT (3) may protect the molecule from MAO metabolism, elevate the brain and circulating levels of an administered dose, and prolong the effects of these molecules without altering the measured parameters for DMT pharmacology. In administrations of DMT and α,α,β,β-d4-DMT (4) at doses of 2.5, 5.0, and 10.0 mg/kg to rats by a subcutaneous route (SC; Barker et al. 1982), resulting analyses (GC/MS) of brain levels of the parent compounds showed that d4DMT (4) attained concentrations 2–3 times greater than DMT itself at the same dose and remained at higher levels as a function of time, remaining detectable in brain at least two times longer. A follow-on study (Beaton et al. 1982) showed that d4DMT (2.5 and 5.0 mg/kg SC) had a shorter time to onset, a greater level of disruption in a food reward behavioral paradigm and a greater duration of action than an equal dose of proteo-DMT. In a similar study, Halberstadt (Halberstadt et al. 2012) examined 5-methoxy-α,α,β,β-d4-DMT (d45MeODMT, 5) versus proteo-5MeODMT and 5MeODMT in combination with the MAO inhibitor pargyline in a behavioral paradigm measuring locomotor activity and patterning. Halberstadt et al. (2008) had previously observed that 1.0 mg/kg 5MeODMT (SC) had biphasic effects on locomotor activity in rats pretreated with a behaviorally inactive dose of the MAOI pargyline (10 mg/kg). Regardless of dose (1.0 mg/kg SC or greater), administration of 5MeODMT alone produced only reductions in locomotor activity, a possible sedative or anxiolytic effect. Although low doses of d45MeODMT (5; 0.3 and 1.0 mg/kg, SC) produced only hypoactivity as well, a dose of 3.0 mg/kg caused a biphasic locomotor profile like that produced by the combination of 5MeODMT and pargyline, a potent MAO-A inhibitor. However, a further contribution of the study was that receptor binding experiments showed that deuterium substitution had little measurable effect on the binding affinity of d45MeODMT for a wide variety of neurotransmitter binding sites.

Taken together, these two studies take advantage of the deuterium kinetic isotope effect (Barker et al. 1982; Halberstadt et al. 2008) to render DMT and 5-MeODMT partially resistant to metabolism by MAO, increase their potency and duration of action while maintaining binding affinity and behavioral effects, creating, essentially, the same pharmacology as seen with the co-administration of these compounds with a MAOI, but without the unwanted additional effects of such a drug on other MAO-sensitive bio-compounds. Thus, the use of deuterium essentially creates a single compound ayahuasca or “pharmahuasca” and could be expected to perform in the same manner, as this “deuterhuasca.” One might also expect that the deuterated analogs of these drugs may also be orally active. However, the oral bioavailability of these compounds has, unfortunately, not yet been examined/published, although there should be every expectation that this will be the case. Nonetheless, “deuterhuasca” could still be administered by any of the other routes as well. Thus, a dxDMT therapeutic could possibly be derived that can be administered orally, or by IM, IV or other routes, require a lower dose for effect, provide a longer duration of action, and avoid the unwanted effects on other systems by not requiring the co-administration of an MAOI. It is also anticipated that d4DMT is resistant to not only MAO-A but also MAO-B. Other deuterated analogs of d4DMT would also be expected to exhibit some of these same characteristics. Research has shown that the beta position deuteration has little to no effect in slowing metabolism by MAO (Boulton and Yu, 1981), suggesting that an alpha, alpha-dideutero analog could be just as effective. Several deuterated species of DMT have been synthesized and have been suggested for use as biochemical probes for understanding the role different positions play in transport, metabolism, binding, and clearance (Morris and Chiao 1993). In this regard, one would also expect that alpha deuteration of other psychedelic DMT-related therapeutics, such as psilocybin, would also make the drug more orally bioavailable, potent, and longer lasting without otherwise altering its pharmacology. In fact, Rands et al. (2020) have submitted a patent application that follows this scenario. The invention relates to compositions comprising DMT, deuterated DMT, and/or partially deuterated DMT or a combination of DMT and 2% or more by weight of one or more deuterated N,N- dimethyltryptamine compounds selected from α,α-dideutero-DMT and α,α,β,β-tetradeutero-DMT. Additional and alternative compositions include a combination of DMT and 2% or more by weight of one or more partially deuterated DMT compound selected from α,β,β-trideutero-DMT, α,β-dideutero-DMT, and α-deutero-DMT. Methods of synthesizing compositions and methods of use of described compositions in treating psychiatric or psychocognitive disorders, such as major depressive disorder, are also provided (Rands et al. 2020).