DMT: Uses, Health Effects, Safety, Risks, and Legal Status

DMT is a Schedule I controlled substance in the United States, meaning it’s illegal to use recreationally. DMT goes by many names, including Dimitri, fantasia, and the spirit molecule. DMT is a potent hallucinogenic drug that can dramatically alter a person’s perspective, consciousness, and sensory experiences. Some people find it transformative and life-affirming to have this experience.

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Federal laws aside, many cities in the United States have decriminalized all entheogenic plants and fungi at the municipal level, including the plants used to produce ayahuasca. In Colorado, state voters passed the Natural Medicine Health Act in 2022 to enable adults to access five psychedelic substances, including DMT, in certified centers under the supervision of licensed guides. Other states have planned similar initiatives, separate from the simultaneous and currently still ongoing process of getting FDA approval for these medicines for the treatment of multiple different health conditions. In the United States, 5-MeO-DMT is also a Schedule I substance, which makes it illegal to manufacture, buy, possess, or distribute (sell, trade, or gift) without a DEA license effective as of January 19, 2011. Acute and chronic administration of DMT significantly increased endogenous levels of striatal 3-MT (3-methoxytyramine, a dopamine extraneuronal metabolite) (Waldmeier et al., 1976).

1. This is also true for extraordinary states of consciousness such as “visions” or spontaneous hallucinations or phenomena such as near-death experiences (NDE).
2. Some people find it transformative and life-affirming to have this experience.
3. In addition to having an almost immediate onset, DMT is also extraordinarily short-acting.
4. In blood, data from 417 (300 patients) individuals were examined, 44 patients and 28 controls were positive for DMT.

What about bad trips?

This decrease in dopamine levels is likely not related to change in synthesis, because no change in norepinephrine levels or turnover rate in the diencephalon were observed (Smith, 1977). It appears as if DMT increases central dopamine turnover and enhances striatal dopamine synthesis in rats (Smith, 1977). 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. Another indication that DMT does not act directly at dopamine receptors is the lack of adenylate cyclase activity in the dorsal striatum of rats (von Hungen et al., 1975). Agonistic properties and affinities for 5-HT1A receptor vary among the classic psychedelics.

How do people take it?

“DMT is not orally active, as are LSD, psilocybin, mescaline—the other classical psychedelics,” said Strassman. If Imperial’s research already has the drug prohibitionists hyperventilating, the model Carhart-Harris proposes for the NHS will is mdma addictive send them into an altered state of consciousness. It is the administration of psilocybin and DMT (not, it should be stated, at the same time) in a series of therapeutic treatments, for those conditions where they are shown to be effective.

The main problem with the theory that DMT is an endogenous sigma-1 receptor agonist is that it requires concentrations in the micromolar range, whereas selective sigma-1R agonists such as (+)-pentazocine have affinities in the nanomolar range (Fontanilla et al., 2009). If DMT is only available in trace amount in humans and is rapidly metabolized (Burchett and Hicks, 2006), how can DMT levels rise enough to account for sigma-1 alcohol abuse and alcoholism receptor-mediated effects? Supporting the role of sigma-1 receptor is that the SSRI fluvoxamine, has sigma-1 receptor agonist properties with higher affinity than DMT. Fluvoxamine works better with patients suffering from psychotic depression compared to antidepressants without sigma-1 receptor agonist properties (Stahl, 2008). Selective sigma-1 receptor agonists do not cause psychotomimetic effects in animals.

“Because it’s a treatment model that requires some psychological preparation, quite a few hours of staff time to look after this patient, and ward space. Participants will lie in the fMRI with an EEG cap on and their eyes closed. The whole experiment the buddhist view on addiction multiple perspectives takes minutes (the duration of a DMT trip), with researchers interjecting regularly to ask them to rate the intensity of the experience. Based on the data available so far, DMT is unlikely to cause tolerance, dependence, or physical addiction.

A review by Frecska and colleagues (2013), suggests that during physical signals of agony, lungs synthesize large amount of DMT (primarily through the removal of INMT inhibitors) and can release DMT into arterial blood within seconds. Once in blood circulation DMT is safe from degradation as extracellular, circulating MAO enzymes deaminate only primary amines (McEwen and Sober, 1967). Through the use of active transport mechanisms already discussed for taking DMT from blood into the brain, could potentially keep brain alive longer without the brain having to produce DMT on its own. Exogenous DMT-like psychedelic effects are in essence similar to subjective reports provided after clinical death and near death experiences. Strassman (2001) believes DMT to be very likely involved in the dying process. DMT does bind to 5-HT1D receptor (Hamik and Peroutka, 1989; Heuring and Peroutka 1987; Pierce and Peroutka 1989) and 5-HT3 receptor (Carbonaro, unpublished data), however little has been investigated to follow these results up.

A recent study indicated that one out of three patients on lithium who took psilocybin (also a classical tryptamine psychedelic) experienced a seizure. The positive effects of DMT can be similar in some regards to other psychedelic substances. However, DMT is subjectively distinct from all other psychedelics with its short-acting and unique characteristics. As with other psychedelics, however, the experience significantly depends on many external variables. These include the ‘set and setting’, mindset of the individual, integration, and preparation, route of administration, dosage, and many other important factors.

Like other classic psychedelics, DMT does induce this head twitch response in C57Bl/6 mice, which is blocked by 5-HT2A inverse agonist, MDL (Carbonaro et al., 2015). However, the overall number of head twitches induced by DMT is much smaller compared to most other psychedelic compounds. DMT failed to produce this head twitch response in Swiss Webster mice (Fantegrossi et al., 2006) These discrepancies may be due to the rapid degradation of DMT or other peculiarities specific to DMT.