OPEN Foundation

M. Gatch

Neuropharmacology of N,N-Dimethyltryptamine

April 25, 2016 / DMT, Neuroscience, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety / By / ,

Abstract

N,N-Dimethyltryptamine (DMT) is an indole alkaloid widely found in plants and animals. It is best known for producing brief and intense psychedelic effects when ingested. Increasing evidence suggests that endogenous DMT plays important roles for a number of processes in the periphery and central nervous system, and may act as a neurotransmitter. 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.

Carbonaro, T. M., & Gatch, M. B. (2016). Neuropharmacology of N, N-Dimethyltryptamine. Brain Research Bulletin. http://dx.doi.org/10.1016/j.brainresbull.2016.04.016

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The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice

July 3, 2014 / Neuroscience, Other subjects, Papers, Psychopharmacology, Publications / By / , , , , ,

Abstract

Rationale

Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens.

Objective

The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT).

Methods

Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT.

Results

MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro.

Conclusions

The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

Carbonaro, T. M., Eshleman, A. J., Forster, M. J., Cheng, K., Rice, K. C., & Gatch, M. B. (2014). The role of 5-HT2A, 5-HT2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N, N-dimethyltryptamine and N, N-diisopropyltryptamine in rats and mice. Psychopharmacology, 1-10. https://dx.doi.org/10.1007/s00213-014-3658-3

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30 April - Q&A with Rick Strassman

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