Author: Gary Jackson

DMT Dimethyltryptamine Abuse Signs & Symptoms of DMT Abuse

The effects of DMT seem to be mostly hallucinogen-like, as it produced only 50% drug-appropriate responding in 3,4-methylenedioxymethamphetamine (MDMA)-trained rats, and produced a maximum of 37% drug-appropriate responding in methamphetamine-trained rats (Gatch et al., 2009). An approach gaining increasing interest within the last decade is to examine interacting roles of serotonin and glutamate in mediating the effects of DMT. Of particular interest are the roles of group II metabotropic glutamate receptors (mGluR2/3), the NMDA receptor, and 5-HT2A receptors in modulating the levels of glutamate in the synapse. These group II glutamate receptors (mGluR2/3) may also be potential target sites for mediating hallucinogenic effects (Gonzalez-Maeso et al. 2007, 2008; Delille et al. 2012; Moreno et al. 2011; Winter et al. 2004). DMT, like other classic hallucinogens increase 5-HT levels and/or decrease the turnover of 5-HT (review Nichols, 2004). DMT increases excretion of IAA and 5-hydroxy IAA in humans (Szara, 1956).

• Generally, acetylcholine levels in brain are reduced when its rate of release or turnover are increased (Haubrich and Wang, 1977).
• Interactions of both TAAR and sigma-1 receptors will be discussed in detail in subsequent sections.
• DMT is found in trace amounts throughout nature, including the human body.
• DMT can be detected as an endogenous compound in urine, blood, and cerebrospinal fluid.
• Therefore, recent evidence that DMT causes changes in human brain activity could be of therapeutic value.

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. 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). Taken together, these findings indicate that serotonergic hallucinogens largely produce discriminative stimulus effects similar, but not entirely identical to those of DMT.

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Generally, acetylcholine levels in brain are reduced when its rate of release or turnover are increased (Haubrich and Wang, 1977). Oxidative deamination of DMT by MAO may not be the sole metabolic pathway in humans (Riba et al., 2012). A study by Gomes et al. (2014) suggests that a different metabolic pathway by which DMT can be oxidized by peroxidases may be responsible for increasing cytotoxic activity of peripheral-blood mononuclear cells (Tourino et al., 2013). Metabolites in this pathway include hydroxy-DMT, N,N-dimethyl-N-formyl-kynuramine, and N,N-dimethyl-kynuramine. Barker et al. (1980) suggest other possible metabolites of DMT include 1,2,3,4-tetrahydro-beta-carboline (THBC) and 2-methyl-THBC. 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).

• When concentrations were reported, not just whether it was present or not present, it ranged from 51 pg/ml (HPLC-radioimmunoassay) to 55 ng/ml (direct fluorescence assay of extracts).
• Although it is rarely reported, some users may develop a psychological addiction to the drug and, as a result, begin to use DMT more often.
• DMT increased levels of corticotropin, cortisol, prolactin, and growth hormone when administered to human volunteers (Strassman et al., 1994).
• DMT reduced inflammation ostensibly via sigma-1 receptor (Szabo and Rajnavdgyi, 2014), and can induce neuronal plasticity, which is a long-term recuperative process that goes beyond neuroprotection (Ruscher et al., 2011; Tsai et al., 2009; Kourrich et al., 2012).

However, no changes in DMT levels were observed in rapidly cycling states (manic-depressive) (Checkley et al., 1980). These findings renewed interest in the transmethylation hypothesis, which states that schizophrenia may be due to stress-induced production of psychotomimetic methylated derivatives of catecholamines or indolealkylamines in the brain. DMT seems to fits the bill as it is an indolealkylamine, is an endogenous compound, and is linked to stress reactivity (see reviews by Myin-Germys and van Os, 2007; Grammenos and Barker, 2015).

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A book describing these results was published in the popular press (Strassman 2001). Strassman concluded that DMT is a powerful tool for self-discovery and understanding consciousness, which may have helped to drive interest in recreational use of DMT and related tryptamine hallucinogens. In recent years, recreational use of DMT has been increasing; for example, Cakic et al., (2010) reported that 31% of recreational DMT users endorse psychotherapeutic benefits as the main reason for consumption. Similar to ayahuasca, recreational users have made similar concoctions referred to as pharmahuasca. 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.

Experimental studies have been few and it is premature to conclude that DMT may have clinically relevant uses. Practitioners traditionally prepare ayahuasca using two plants called Banisteriopsis caapi and Psychotria viridis. The latter contains DMT while the former contains MAOIs, which prevent certain enzymes in your body from breaking down DMT. Many South American cultures use ayahuasca in religious and spiritual ceremonies and have done so for centuries. ‘Set’ refers to a person’s mind-set including their mood, thoughts and expectations.

DMT Side Effects

The 5-HT2A receptor is thought to be the primary target of classic serotonergic-mediated psychedelic compounds, such as LSD, DOI, psilocin, and mescaline, although 5-HT1A and 5-HT2C receptors may also play some role (Aghajaian and Marek, 1999a, 1999b; review Nichols 2004). When DMT was administered to squirrel monkeys (2 mg/kg, i.m.) for days, it failed to elicit tolerance to the disruption of responding maintained on a fixed-ratio schedule of food reinforcement (Cole and Pieper, 1973). Similarly in cats, Gillin et al. (1973) demonstrated that DMT (3 mg/kg, i.p.) did not produce tolerance when administered 7-15 days twice daily or every 2 or 24 hours to its effects on EEG, pupil dilation, coordination, posture, and other physical signs. To the contrary, an increase in sensitivity to repeated injections were observed. However, following administration of higher doses of DMT and more frequent injections, partial tolerance to DMT in rats occurred with dose ranges of 3.2 – 10 mg/kg every 2 hours for 21 days (Gillin et al., 1973).

• Although DMT occurs naturally in plants, it can also be synthesised chemically, producing DMT in its base or salt form.
• Similar to ayahuasca, recreational users have made similar concoctions referred to as pharmahuasca.
• It has been proposed that DMT is an endogenous anxiolytic compound through its actions at the trace amino acid receptor (Jacob and Presti, 2005).

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). These three mechanisms may yield high intracellular and vesicular concentrations within neurons (Frecska et al., 2013), which suggests that DMT may have a biological role.

Serious side effects occur more frequently if you have pre-existing mental health or physical conditions. 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.