Exogenous DMT formulations containing a reversible MAOI (such as ayahuasca) can result in blood levels up to 1.0 mg/ml or higher (Dos Santos, 2011). On average a 100 mL dose of ayahuasca contains about 24 mg of DMT (Callaway et al., kratom abuse symptoms: signs and dangers to watch for 1996). Interestingly, DMT is itself a short-acting monoamine oxidase inhibitor at high doses (maximum effects at 50 mg/kg), and is selective for MAO-A (Reimann and Schneider, 1993, Smith et al., 1962; Waldmeier and Maitre, 1977).
Evidence in mammals
Retrospective assessment of ‘Immersion’, ‘Entity encounters’, ‘Ego dissolution’ and ‘Visual imagery’ over continuous infusions of placebo and different doses of DMT (minutes 0–30). DMT infusions induced sustained effects of ‘Immersion’, ‘Entity encounters’ and ‘Visual imagery’, while ‘Ego-dissolution’ remained low across doses. In mammals, the psychoactive effects produced by DMT seem to be largely mediated by the 5-HT2AR, although the complex subjective effects reported by DMT users are likely modulated by other receptor systems such as the metabotropic glutamate receptors.
How long does DMT last? Effects on the body and more
While research into N,N-Dimethyltryptamine (DMT) suggests potential therapeutic benefits, it’s important to approach its use with caution, recognizing the powerful effects and legal status of DMT varies by jurisdiction. The prolonged or sustained effects of DMT, despite its short pharmacological half-life, may be attributed to these profound psychological and neuroplastic changes that persist well beyond the immediate effects of the drug. This suggests that the profound, often mystical experiences induced by DMT play a critical role in its therapeutic potential. Recent studies have begun to explore its potential, particularly in treating depression and anxiety, marking a pivotal moment in psychedelic research. DMT may also worsen preexisting psychological conditions, particularly schizophrenia. Though rare, hallucinogens can also cause persistent psychosis and hallucinogen persisting perception disorder (HPPD).
Physical health risks
The bolus doses produced a rapid, marked, and short-lasting increase in blood pressure and heart rate that peaked within 2 min (Table 1, Supplementary Fig. S1). DMT infusions only mildly and nonsignificantly elevated blood pressure and heart rate compared with placebo. DMT induces its subjective effects primarily via the activation of serotonin 5-hydroxytryptamine 2A receptors, similar to other classic psychedelics, including lysergic acid diethylamide (LSD) and psilocybin [21]. LSD and psilocybin-induced endocrine effects, including increases in circulating oxytocin [22,23,24] and brain-derived neurotrophic factor (BDNF) [23, 25, 26], that may contribute to their therapeutic effects or be useful as biomarkers in patients [27].
The drug has no known medicinal uses, and it can only be legally obtained for research purposes with special permissions from the DEA and the Food and Drug Administration (FDA). The Drug Enforcement Administration (DEA) classifies DMT as a Schedule 1 substance. This means it is illegal to buy, distribute, manufacture, or possess DMT in the United States. “As a result, I was forced to ask for help — something I struggled with doing in my life, having developed hyper-independence as a trauma response. This experience was initially terrifying for me but ultimately became comforting as I eventually learned to feel safe asking for help and trusting that it would be there for me. Internationally DMT is illegal, but ayahuasca and DMT brews and preparations are lawful.
This aligns with a previous study of the brain response to psilocybin published by senior author Robin Carhart-Harris. The most significant changes were detected in brain areas linked to high-level cognitive functions like imagination. Experts have suggested other receptors in the brain may also play a role, such as the sigma-1 receptor, is marijuana addictive or that a presently unknown hallucinogenic receptor may be at work. She is in a treatment room at the Imperial College Clinical Research Facility in London, taking part in a scientific study into the effects of illegal hallucinogen DMT. The lights are dimmed and a specially commissioned ambient soundtrack plays in the background.
- Interestingly, DMT is itself a short-acting monoamine oxidase inhibitor at high doses (maximum effects at 50 mg/kg), and is selective for MAO-A (Reimann and Schneider, 1993, Smith et al., 1962; Waldmeier and Maitre, 1977).
- The evaluation consists of 11 yes or no questions that are intended to be used as an informational tool to assess the severity and probability of a substance use disorder.
- One study determined that injected DMT reaches its peak concentration in the blood within 10 to 15 minutes and is below the limit of detection within 1 hour.
- The MAOIs in ayahuasca allow DMT to be gradually absorbed into the brain over a period of 4-6 hours.
DMT increases excretion of IAA and 5-hydroxy IAA in humans (Szara, 1956). Other studies have reported an increase in 5-HT and a decrease in 5-hydroxy IAA after DMT administration (Freedman et al., 1970; Randic and Padjen, 1971). DMT seems to have no effect on tryptophan hydroxylase (Andén et al., 1971), but produces a main effect on the rate of 5-HT turnover (Gillin and Wyatt, 1976). DMT inhibited SERT transport and VMAT2, acting as a substrate and not as an uptake blocker. To establish that DMT acts as a neurotransmitter rather than merely being a by-product of the metabolism of other bioactive molecules, it is necessary to establish that it is synthesized, stored, and released. It is of interest that DMT can pass through three barriers with the help of three different mechanisms so that it can be compartmentalized and stored with the brain (described in detail below).
The cardiovascular effects preclude the use of pure DMT; however, ayahuasca and other DMT-containing ritual beverages seem to be less toxic while retaining the psychological effects. Based on studies of the health status of ayahuasca users, the use of ayahuasca may be safe and even beneficial (e.g., Barbosa et al., 2012; others from below). DMT lacks direct dopaminergic properties, since it did not stimulate dopamine (DA)-sensitive adenylate cyclase (von Hungen et al., 1975). This finding is in agreement with data from a behavioral technique often used to assess direct dopamine agonist effects, which records turning behavior in unilateral nigro-striatal lesioned rats.
Although sources such as SAMHSA report that many individuals who misuse hallucinogens typically stop using them on their own without formal treatment, the development of any substance use disorder represents a potentially serious mental health disorder. The primary aim of the study was to explore the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a fast-acting psychedelic, on mental health outcomes in healthy volunteers. Timmermann et al. conducted a study evaluating the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on mental health outcomes in healthy volunteers yielded significant findings across various psychological measures. When given to human subjects, DMT produces complex visual and auditory hallucinations and increases cortisol levels (Strassman 1994; 1996), which supports its possible role as a possible mediator of schizophrenia.
DMT partially blocked the discriminative stimulus effects of phencyclidine, which produces hallucinations through its actions at NMDA receptors (West et al., 2000). In addition, activation of sigma-1 receptor by DMT may lead to potentiation of NMDA receptors (Cozzi et al., 2009). Electrophysiological studies suggest that stimulation of 5HT2A receptors in the medial prefrontal cortex increases pyramidal cell activity and may stimulate corticotegmental glutamatergic projection neurons (Aghajanian and Marek, 1997). A possible 3 ways to pass a urine drug test explanation for these effects is that mGlu2 receptors co-localize with 5-HT2A receptors to form heteroreceptor complexes (Delille et al. 2012; Gonzalez-Maeso et al. 2007; 2008). It has been suggested that the heteroreceptors induce a psychedelic-specific second messenger cascade (Gonzalez-Maeso et al., 2007; 2008), although this has not been definitively established (Delille et al., 2012). DMT, like other classic hallucinogens increase 5-HT levels and/or decrease the turnover of 5-HT (review Nichols, 2004).
The dosing regimens included two different continuous infusion doses (0.6 and 1 mg/min over 90 min) and combinations of initial loading bolus doses (15 or 25 mg), followed by 90-min DMT infusions as proposed previously [4]. We repeatedly assessed subjective and cardiovascular effects during the subjects’ experience over time and thereafter. We also repeatedly sampled blood and determined plasma levels of DMT [20] to characterize the pharmacokinetics of intravenous DMT. Importantly, although subjective ratings of intensity largely followed plasma concentrations of DMT during the first 20 min, a decoupling was observed from minute 20 onwards. While subjective intensity of drug effects decreased after an initial peak and remained stable with a slight downward slope for the remainder of the infusion, plasma levels of DMT generally increased throughout the infusion. These findings may suggest a progressive development of acute psychological tolerance to DMT during continuous infusion, a finding not seen in previous studies employing this compound.
Therefore, the pharmacokinetic model used for this study has scope for improvement. Our team has since collected further plasma DMT data, including a previous study (Timmermann et al., 2019), which has been used to model the relationship between DMT pharmacokinetics and effects (Eckernäs et al., 2022b, 2023). Psychedelics present an intriguing challenge in psychiatry as their psychological response is known to be highly variable and, at times, unpredictable. This unpredictability is usually accounted for by both dose and so-called non-pharmacological, or contextual variables, commonly described as (mind-) ‘set’ and ‘setting’ (Hartogsohn, 2016). The high variability of plasma DMT concentrations for a single dose in this study suggests that the subject-specific PK profile may significantly influence the psychological response as well.