When smoked or injected intravenously, DMT causes a very rapid, very intense psychedelic experience which lasts a few minutes. Users report the feeling of being ripped from their bodies, and thrown through space at incredible speeds.
DMT produces intense visual and auditory hallucinations of otherworldly landscapes, hidden dimensions and god-like beings. It often produces deep introspection in its users, allowing the revisitation of past memories and providing a fresh perspective on life. Not everyone enjoys these effects, though. Other negative side effects of DMT include:. Like most hallucinogens, DMT has the potential to take you on a bad trip, which can be overwhelming and terrifying.
People have reported being left shaken by a bad DMT trip for days, weeks, and even months. DMT may also worsen preexisting mental health conditions, particularly schizophrenia. Hallucinogens also carry a small risk of persistent psychosis and hallucinogen persisting perception disorder HPPD , according to the National Institute on Drug Abuse.
Increased heart rate and blood pressure are both side effects of DMT, which can be bad news if you already have a heart condition or high blood pressure. Using DMT while taking antidepressants , especially monoamine oxidase inhibitors MAOIs , can result in a serious condition called serotonin syndrome.
Research on its long-term effects is limited. Based on the data available so far, DMT is unlikely to cause tolerance, dependence, or physical addiction. People who regularly use DMT may crave it psychologically, but this is based on anecdotal reports. However, things can get a little muddy when it comes to the plants that contain DMT, like those used to make ayahuasca. These are legal to possess in some countries, including Brazil, Peru, and Costa Rica. Make sure you know about any potential interactions with other substances you use, including any medications.
Call or head to the nearest emergency room if you or someone else experiences any concerning symptoms. Adrienne Santos-Longhurst is a freelance writer and author who has written extensively on all things health and lifestyle for more than a decade. The pharmacokinetics of most anesthetics are best fitted to either a two- or three-compartment model Shafer and Gregg, Since DMT turns out to be best fitted to a two-compartment model see later , only this type will be described here Figure 1.
Figure 1. Structure of a standard two-compartment plus effect site pharmacokinetic model with transfer and elimination rates. Drug is introduced into the central compartment to rapidly achieve a plasma concentration, C T , dependent on the volume of distribution, V C. The drug is removed from the central compartment, quantified by a drop in plasma concentration over time, by both elimination and equilibration with the peripheral compartment.
This rate of plasma concentration decline is controlled by the elimination rate constant, k 10 , and the relative rates of movement from the central to the peripheral compartment, k 12 , and in the opposite direction, k The overall rate, R T , obeys the differential equation:. Complete equilibration with the peripheral compartment is reflected in the exponential term decaying to zero and the steady state elimination rate, R SS , is:. Transfer from the central compartment to the effect site, R 1 E , is generally modeled as a first-order process with rate constant, k 1 e :.
To maintain a constant plasma, and thus effect site, concentration, the infusion rate must equal the overall removal rate, R T. Since this is not constant, except at steady state, the infusion rate must be adjusted to approximate the decline in R T over time. This requires the determination of the pharmacokinetic parameters: V C , k 10 , k 12 , and k 21 , which can be achieved by fitting time-series blood sampling data to a pharmacokinetic model.
To establish that the pharmacokinetics of DMT make it suitable for target-controlled infusion, we used DMT plasma concentration data from a previous study Strassman and Qualls, The details are provided in the original paper. Blood samples were drawn before the infusion and at 2, 5, 10, 15, 30, and 60 min from the end of the infusion 45 s after the infusion began. A total of nine subjects were used in the analysis 9 sets each of 0. These time-series data were fitted to one-, two-, and three-compartment pharmacokinetic models.
This curve is then fitted to a pharmacokinetic model. However, methods taking into account both fixed and random effects on the dose-response—for example, non-linear mixed effects modeling NON-MEM —often give more reliable parameter estimates.
These methods also allow identification of parameter covariates, such as weight or age Mould and Upton, Using the Matlab Simbiology toolkit Mathworks, Inc.
Both datasets were best fitted to a two-compartment model with enzymatic clearance, consistent with Michaelis-Menten kinetics Figure 2.
Table 2 shows the population parameter estimates obtained. Figure 2. Fitting of two-compartment model with enzymatic clearance to blood sample data. Table 2. Fitted pharmacokinetic parameters for 2-compartment model with enzymatic clearance. The mean coefficients of variation in plasma DMT concentration, between 2 and 30 min post-infusion, across the 0. There was also variation in the estimated parameters depending on the dose. Since 0. Therefore, the 0.
However, comparable results were obtained using the alternative parameter set. Having established the model parameters, we then sought to extend the model to include the effect site brain concentration. The model was simulated using an infusion protocol employed in the original study i. While subjects were unable to communicate during the peak DMT effects, a number of observations indicated that these peak effects in each subject occurred at approximately 3 min from the beginning of the infusion.
First, the lower doses of drug 0. With these lower doses, effects peaked at approximately 3 min, began dissipating quickly, and were resolved by 15—20 min. That the time course of peak DMT blood levels is identical across the spectrum of doses suggests that the correspondence between the time course of peak DMT effects and peak plasma levels at higher incapacitating doses also holds true.
Acute autonomic responses to DMT also reached their highest levels between 2 and 5 min from the end of the infusion, usually at the former time point. These included pupil diameter, heart rate, and mean arterial blood pressure. At the peak effect time, the drug concentration in the central compartment is equal to the concentration at the effect site. This makes it straightforward to model the effect site concentration using the first-order rate equations:.
The resulting simulation is plotted in Figure 3 and seems to fit the observations well. Figure 3. Simulated time course of DMT brain concentration following a 0. Typically, the subject would appear to transition into full dissociation from the external world toward the end of the 15 s saline flush following the 30 s DMT infusion. Clinical observation of the subjects appears to match this time course, with their maximum level of absorption in the subjective experience occurring at 4—5 min, likely as the initial rush and disorientation began to subside.
For example, subjects demonstrated seemingly involuntary deep rhythmic breathing, the mouth being open in a passive regressed manner, and REM-like eye movements behind closed lids. Conversely, subjects appeared to be less under the influence of a high dose of DMT as early as 5 min; e.
However, lower or higher concentrations can be achieved using an analogous protocol with modified infusion rates. We developed our infusion model using the bolus-elimination-transfer B. An initial bolus, B 0 , is used to rapidly bring the plasma concentration to the desired level, C T :. The infusion rate is then calculated to equal the sum of the elimination rate, E , and the transfer rate from the central to the peripheral compartment, T.
The sum of E and T gives the overall infusion rate as defined earlier:. Since the model-fitting established that E is dominated by enzymatic clearance, k 10 must be reformulated in terms of Michaelis-Menten kinetics:. Since the first term in the R T equation depends only on the plasma concentration, it becomes constant when a steady state concentration is reached.
The exponential term is only important before steady state is reached, in the initial stage of the infusion. It then decays to zero. Assuming the steady state concentration is the desired effect site concentration, C T , the maintenance infusion rate, R ss , can be calculated:. Using the estimated model parameters, this gives a steady state infusion rate of 0. However, during the first few min of the infusion, the exponential term is large; i. This rate of transfer peaks at 3.
The infusion rate must be set to compensate for this transfer, being decreased gradually until R ss is reached. This variable infusion rate is essential to attaining and maintaining a stable effect site concentration.
If the initial rate is too low following the initial bolus, the effect site concentration plummets well below that desired and is not maintained. Conversely, if a high initial infusion rate is maintained, the effect site concentration continues to increase. It is possible that this accounts for the relatively high rate of volunteers dropping out of the Gouzoulis-Mayfrank study Gouzoulis-Mayfrank et al.
To examine the possibility of effect site concentration overshoot, we performed simulations using the Gouzoulis-Mayfrank infusion protocol: 0. Figure 4 shows the expected effect site concentration over this infusion period for a 75 kg subject. This is a very high concentration and is certain to produce extremely intense effects in almost all individuals. Figure 4. Simulated time course of plasma and effect site DMT concentration using the Gouzoulis-Mayfrank et al.
The infusion begins at 2 min at a rate of 4. The infusion is updated every min, and decreases according to the peripheral transfer rate decay the exponential term in the R T equation.
Steady state does not occur until after 20 min of infusion, after which a constant maintenance infusion rate of 0. Figure 5. Witnessed written informed consent was obtained from all subjects, and confidentiality and anonymity were maintained throughout the study. The phenomenological content of dream states Schredl and Hofmann, ; Kahan and Laberge, ; Thomas et al. However, whilst the endogenous human hallucinogen DMT reliably and reproducibly generates one of the most unusual states of consciousness available, its phenomenology has only begun to be characterized.
One of the reasons for this is its short duration of action. A technology for extending DMT experiences in a controlled manner beyond what is achievable using bolus administration therefore would be of great value. Modern target-controlled infusion protocols employ algorithms that allow the infusion rate to be calculated and adjusted in real time, such that the effect site drug concentration can be raised and lowered in order to control, for example, the level of anesthesia Bailey and Shafer, ; Shafer and Gregg, Our analysis highlights the potential of using the target-controlled infusion methodology for extended DMT sessions.
Using time-series blood sampling data and pharmacokinetic modeling, we propose that the unique pharmacological characteristics of DMT make it suitable for administration by target-controlled intravenous infusion. These characteristics include a rapid and short-acting effect, and lack of acute tolerance to its subjective effects.
Such methods could be used to control the depth of the experience during a DMT session, moving the subject into more intense levels of DMT intoxication or lowering them back into more manageable levels to provide both respite and easier communication with the research team.
The methodology developed here is the first step toward a protocol that is ready for use in research subjects. The purpose of this modeling is to provide a proof-of-principle that the pharmacokinetic and pharmacodynamic properties of DMT are such that stable effect site concentrations can be achieved using target-controlled infusion. More extensive sampling and more detailed pharmacokinetic modeling are required to establish definitive population parameters, the extent of inter- and intra-subject variability, and covariates.
As with any drug administered by target-controlled infusion, subject covariates including weight, age, gender, and liver function create significant inter-subject and intra-subject variability in the dose-concentration response White et al. In this study, the mean coefficients of variation in plasma DMT concentration across the 0.
However, the response variability for continuous infusion protocols is always lower than that observed for bolus injection Hu et al. For this reason, most anesthesia infusion protocols undergo a number of iterations as pharmacokinetic models are updated and refined. Thus, the variability observed in this initial modeling study does not preclude the development of a target-controlled infusion protocol for DMT. In addition, despite the large dose-concentration variability, the variability in the relationship between the dose and the subjective response was much lower.
Therefore, the target concentration accuracy typically achieved with anesthetic agents is likely to be suitable in a DMT infusion protocol. The phenomenology of the ayahuasca state has been the subject of more extensive analyses than that of pure DMT Shanon, However, to render the preparation orally-active, the ayahuasca brew must contain both a DMT-containing plant as well as one containing a beta-carboline MAO inhibitor, such as harmaline McKenna et al.
Since beta-carbolines themselves possess psychoactive properties and may potentiate the effects of other psychoactive alkaloids in the plant mixture Callaway et al. Furthermore, it is not possible to precisely regulate and maintain the effect-site DMT concentration with an oral preparation. There are a number of research questions that a successful application of target-controlled IV infusion of DMT may address. For example, the maximum DMT effect may extend further than what has been previously described in bolus studies.
Very high acute doses of DMT typically produce a delirium, and users are unable to recall details of the experience. However, this may result from too rapidly attaining supra-maximal concentrations of drug. Using the method described here, it may be possible to move the individual gradually into a greater level of intoxication while maintaining the characteristic mental clarity associated with fully psychedelic doses. In addition, this model is applicable to studies of the neural correlates of the psychedelic state as revealed by modern functional neuroimaging techniques, which are also of great interest Carhart-Harris et al.
Since such protocols usually require the research subject to be under the influence of the drug for an extended period of time, our methodology would benefit these investigations as well. Finally, there are potential psychotherapeutic applications. With the resumption of clinical research with psychedelic drugs, projects confirming and extending early research demonstrating the benefit of psychedelic drug-assisted psychotherapy are playing a prominent role.
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