Author: Alex Thompson

DMT: Side effects, facts, and health risks

This is likely due to rapid degradation by peripheral monoamine oxidase (MAO), the enzyme (located in mitochondria) responsible for catalyzing the oxidative deamination of endogenous biogenic amines (McKenna et al., 1984). In order for DMT to be bioavailable, oral formulations such as ayahuasca contain Banisteriopsis caapi and other beta-carboline harmala alkaloids that act as MAOIs (Schultes, 1972; Shulgin, 1976; Der Marderosian et al., 1968; Agurell et al., 1968). MAO-A inhibitors such as iproniazid prolongs the half-life of DMT in rat brain (Lu et al., 1974), and can extend the time course effects of DMT in drug discrimination from 30 min to 60 min (Gatch, unpublished data). 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).

1. It is present in cohoba, a hallucinogenic drug derived from the seeds of Piptadenia peregrina.
2. According to the CDC, synthetic opioids like fentanyl are among the leading causes of overdose deaths.
3. Reviews of this early research concluded that the data was suggestive but not conclusive (e.g., Gillin et al., 1976).
4. Though DMT has received increasing media attention, the compound is currently illegal in the U.S.

The 5-HT2C receptor is likely less significant in the psychedelic effects since tolerance develops to the 5-HT2C receptor (Smith, 1998). Little or no tolerance is developed to the subjective effects of DMT in clinical studies (Strassman, 1996). Despite its very short duration of action, DMT can be trained as a discriminative stimulus (Gatch et al., 2009). In addition, although DiPT fully substituted in DMT-trained rats (Gatch et al., 2011), DMT only produced 65 % DAR in DiPT-trained rats (Carbonaro et al., 2013).

Many South American cultures use ayahuasca in religious and spiritual ceremonies and have done so for centuries. As DMT has been shown to have slightly better efficacy (EC50) at human serotonin 2C receptor than at the 2A receptor,[162][163] 5-HT2C is also likely implicated in DMT’s overall effects.[172][177] Other receptors such as 5-HT1A[161][172][174] and σ1[168][178] may also play a role. If someone does not address serotonin syndrome, it can cause life threatening complications, including seizures, kidney or respiratory failure, or loss of muscle tissue.

DMT is a Schedule I controlled substance in the United States, which means it’s illegal to make, buy, possess, or distribute it. Some cities have recently decriminalized it, but it’s still illegal under state and federal law. Since DMT is illegal, there is limited research that shows any benefits. These benefits remain prospective and experimental, not scientifically proven. DMT could have serious adverse consequences for users with pre-existing psychological problems or a mental illness, such as schizophrenia. Mental side effects may linger for many days or weeks after ingestion of the drug.

It will then examine evidence regarding the neuropharmacological effects of DMT, from both behavioral studies of the exogenous effects of DMT, and from molecular studies of sites of action of endogenous DMT. Next, the review will turn to the use of DMT both as a model for various disorders and the use of DMT to treat some of these disorders. The review will conclude with the effects of DMT on other organ systems besides the central nervous system.

Drugs & Supplements

When a 5-HT1A antagonist, pindolol, was co-administered with DMT, the increase in heart rate was diminished whereas the increase in blood pressure was enhanced (Strassman, 1996). Tolerance to the effects of DMT was tested by administration of DMT to human volunteers four times at 30-min intervals. A progressive decrease in heart rate was observed over the four doses, but not in blood pressure (Strassman, et al., 1996). In contrast, two repeated doses of ayahuasca 4-h apart reduced systolic blood pressure and heart rate (Dos Santos et al., 2012). Long-term use of DMT-containing beverages may be of more concern as 14-day exposure to ayahuasca in rats altered the structure of the aorta, leading to a thickening of the walls of the aorta relative to the lumen diameter (Pitol et al., 2015). The wide use of DMT in the form of ayahuasca for many years has led to a number of studies focusing on adverse health effects or potential benefits of ayahuasca use.

This paper reviews the current literature of both the recreational use of DMT and its potential roles as an endogenous neurotransmitter. Pharmacokinetics, mechanisms of action in the periphery and central nervous system, clinical uses and adverse effects are also reviewed. DMT appears to have limited neurotoxicity and other adverse effects except for intense cardiovascular effects when administered intravenously in large doses. Because of its role in nervous system signaling, DMT may be a useful experimental tool in exploring how brain works, and may also be a useful clinical tool for treatment of anxiety and psychosis. If DMT is stored in synaptic vesicles,[169] such concentrations might occur during vesicular release.

These are of capsules containing free-base DMT and some monoamine oxidase inhibitors (MAOI) such as synthetic harmaline (Ott, 1999) or Syrian Rue (rich in beta-carbolines; Brierley and Davidson, 2012). The classic positive symptoms of schizophrenia include delusions and hallucinogens, so hallucinogenic compounds seem an obvious tool for modeling schizophrenia. Given that hallucinogens produce their effects primarily through activation of the 5-HT2A receptor (review Nichols, 2004), the serotonin system provides an alternative to the dopamine model of schizophrenia. The dopamine model has produced a wide range of treatment medications which are very useful, but do not fully treat the range of symptoms experienced during psychotic episodes and produce substantial adverse effects.

5. Detection of endogenous DMT in blood, urine, and cerebrospinal fluid

Formation of IAA was thought to be likely due to oxidase deamination of NMT (Barker et al., 1980), but was later established to be also in part by direct deamination by MAO (Barker et al., 1982). The putative roles of DMT will be explored in more detail in subsequent sections of this review. The review will begin by addressing the basic mechanisms of action of DMT, both pharmacokinetic and pharmacodynamic.

Jacob and Presti (2005), and others have suggested that the effects of endogenous DMT are mediated via sigma receptor roles (see review by Grammenos and Barker, 2015 or refer to section in this review). As previously mentioned, DMT interacts with a variety of ionotropic and metabotropic receptors. The subjective effects of large doses of exogenous DMT are most likely mediated primarily by 5-HT2A receptors, with 5-HT2C receptors playing little or no role. MGlu2/3 receptors have significant modulatory effects, and the interaction of serotonergic and glutaminergic receptors may play a central role. DMT does not have direct effects on DA receptors, but indirectly alters the levels of dopamine, with resulting neurochemical and behavioral effects. Finally, DMT may be an endogenous ligand at TAAR and sigma-1 receptors, but at the least, the effects of DMT at these receptors may play important physiological roles.

These high concentrations are similar to those observed in the synapse when endogenous DMT is released (review, Wallach, 2009). In addition, molecular effects of DMT have been identified that are not mediated by serotonin receptors. For example, DMT-enhanced phosphatidylinositol production is not blocked by 5-HT2A receptor antagonists (i.e., ketanserin; Deliganis et al., 1991). More recent hypotheses for molecular roles of endogenous DMT have developed over the last decade, and include the potential involvement of TAAR (mentioned above) and sigma-1 receptors. Interactions of both TAAR and sigma-1 receptors will be discussed in detail in subsequent sections. 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.

Can You Become Addicted to DMT?

Thus, while in vitro receptor binding affinities, efficacies, and average concentrations in tissue or plasma are useful, they are not likely to predict DMT concentrations in the vesicles or at synaptic or intracellular receptors. Under these conditions, notions of receptor selectivity are moot, and it seems probable that most of the receptors identified as targets for DMT (see above) participate in producing its psychedelic effects. Doses of ayahuasca 15 or 30-fold higher than commonly used ritual doses increased serotonergic neurotransmission (Pic-Taylor et al., 2015). Long-term ayahuasca users show difference in midline brain structures using MRI versus matched controls (Bouso et al., 2015).

Find Hallucinogen Addiction Treatment Programs

People who sell them often lace DMT with additional substances as they can produce a stronger trip. DMT may be an agent of significant adaptive mechanisms that can also serve as a promising tool in the development of future medical therapies (Frecska et al., 2013). There have been proposals that DMT might be a useful treatment of anxiety, substance abuse, inflammation, or for cancer. Experimental studies have been few and it is premature to conclude that DMT may have clinically relevant uses. This can lead to a potentially life threatening condition called serotonin syndrome disorder. DMT users frequently claim that it has fewer side effects than other psychedelic drugs, but this is a difficult claim to measure and quantify.

Evidence in mammals

It is present in cohoba, a hallucinogenic drug derived from the seeds of Piptadenia peregrina. This means that it is illegal to manufacture, buy, possess, or distribute the drug. The substance has a high potential for abuse, no government-recognized medical use, and a lack of accepted safety parameters for use. Know that DMT is a very powerful compound that can have a dramatic effect on your consciousness.

Concentrations in urine range from 0.02 to 42.98 +/-8.6 (SD) ug/24h, and from 0.16 to 19 ng/ml. In blood, data from 417 (300 patients) individuals were examined, 44 patients and 28 controls were positive for DMT. Like detection in urine, extraction methods and analytical approaches were highly inconsistent.