Brain Research Bulletin
April 30, 2016
Theresa M. Carbonaro, Michael B. Gatch
258 citations
N,N-dimethyltryptamine (DMT) is an indole alkaloid found in plants and animals, known for producing brief, intense psychedelic effects. Evidence suggests endogenous DMT may act as a neurotransmitter in the periphery and central nervous system. This review covers recreational use, potential endogenous roles, pharmacokinetics, mechanisms of action, clinical uses, and adverse effects. DMT appears to have limited neurotoxicity and few adverse effects, except for intense cardiovascular effects when given intravenously in large doses. It may be a useful experimental tool for exploring brain function and a clinical tool for treating anxiety and psychosis.
Psychopharmacology
July 2, 2014
Theresa M. Carbonaro, Amy J. Eshleman, Michael J. Forster et al.
67 citations
The 5-HT2A receptor plays a major role in mediating the effects of the hallucinogens DMT and DiPT. A 5-HT2A receptor inverse agonist fully blocked the discriminative stimulus effects of DMT but only partially blocked those of DiPT. A 5-HT2C receptor antagonist partially attenuated DiPT's effects but minimally affected DMT. An mGluR2/3 agonist produced potent but partial blockade of DMT's effects, while an mGluR2/3 antagonist facilitated the effects of both compounds. Both DMT and DiPT induced head twitches, with DiPT producing more, and these were blocked by a 5-HT2A receptor inverse agonist. DiPT acted as a low-potency full agonist at the 5-HT2C receptor in vitro. The findings suggest that 5-HT2C and mGluR2 receptors modulate the effects of these tryptamine hallucinogens to some degree.
Journal of Pharmacology and Experimental Therapeutics
April 8, 2011
Michael B. Gatch, Michael J. Forster, Aaron Janowsky et al.
42 citations
Three synthetic hallucinogens—DIPT, 5-MeO-DET, and 5-MeO-AMT—produced behavioral effects in rats similar to those of known abused hallucinogens like LSD and DMT, but not to psychostimulants like cocaine or methamphetamine. DIPT fully substituted for DMT and DOM, while 5-MeO-DET fully substituted for DMT; none fully substituted for cocaine or methamphetamine. All three compounds acted at serotonin 5-HT(1A) and 5-HT(2A) receptors and blocked serotonin reuptake. 5-MeO-AMT also weakly released serotonin and blocked dopamine uptake. DIPT and 5-MeO-DET may have abuse liability similar to hallucinogens and were hazardous at high doses, causing activity and lethality.
Behav Pharmacol
August 1, 2017
Michael B. Gatch, Sean B. Dolan, Michael J. Forster
36 citations
Four novel synthetic hallucinogens (25B-NBOMe, 25C-NBOMe, 25I-NBOMe, and 5-MeO-DALT) were tested in rats and mice for their behavioral effects. 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe reduced locomotor activity in mice, while 5-MeO-DALT increased activity at 10 mg/kg but suppressed it at 25 mg/kg. In rats trained to discriminate the hallucinogen DOM or the entactogen MDMA, 25B-NBOMe fully substituted for both drugs at 0.5 mg/kg, but higher doses reduced drug-appropriate responding. 25C-NBOMe fully substituted for DOM but only partially for MDMA. 5-MeO-DALT fully substituted for DOM but not MDMA. 25I-NBOMe failed to fully substitute for either, likely due to its strong rate-depressant effects. The compounds appear attractive for hallucinogenic use but less so as MDMA substitutes, and their abuse potential matches that of scheduled compounds.
ACS Pharmacology & Translational Science
December 29, 2020
Michael B. Gatch, Adam C. Hoch, Theresa M. Carbonaro
13 citations
Eight novel substituted tryptamines produced hallucinogen-like effects in rats trained to discriminate the hallucinogen DOM from saline. All compounds fully substituted for DOM, with potencies equal to or less than DOM. Four compounds—4-OH-MET, 4-OH-DET, 4-OH-DMT, and 4-AcO-DMT—reduced response rates at fully substituting doses. Because these compounds mimic DOM's discriminative stimulus effects, they may carry similar abuse liability. 4-Acetoxy substituted compounds were less potent than 4-hydroxy ones, and N,N-diisopropyl compounds were less potent than those with dimethyl, diethyl, N-methyl-N-ethyl, or N-methyl-N-isopropyl groups.
Behavioural Pharmacology
June 1, 2020
Michael B. Gatch, Sean B. Dolan, Michael J. Forster
6 citations
Most synthetic cathinones tested produce effects similar to the club drug MDMA in rats, but not all. In rats trained to distinguish MDMA from a placebo, six of seven cathinones—4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone—fully substituted for MDMA's discriminative stimulus effects. Methcathinone produced at most 43% MDMA-like responding, and higher doses suppressed responding. The potency of MDMA-like versus psychostimulant-like effects varied substantially among compounds, indicating that some synthetic cathinones are more MDMA-like than psychostimulant-like. This variability suggests that cathinones with MDMA-like effects may be more likely used as club drugs.
Drug and Alcohol Dependence Reports
August 10, 2023
Rebecca D. Hill, Ritu A. Shetty, Nathalie Sumien et al.
4 citations
Three synthetic benzofurans—5-APDB, 5-MAPB, and 6-APB—were tested in mice and rats to compare their behavioral effects with MDMA, cocaine, and methamphetamine. In mice, 6-APB produced strong locomotor stimulation 20 to 50 minutes after injection, while 5-MAPB caused modest stimulation, and 5-APDB initially depressed then modestly stimulated activity. All three compounds were more potent than MDMA. In rats trained to discriminate MDMA from saline, all three benzofurans fully substituted for MDMA, indicating similar subjective effects. Only 5-MAPB fully substituted for cocaine, and none fully substituted for methamphetamine. The findings suggest these benzofurans may have abuse liability as substitutes for MDMA.
Behav Pharmacol
December 6, 2024
Daaniyal D. Munir, Ritu A. Shetty, Michael B. Gatch et al.
1 citation
Four novel synthetic hallucinogens structurally similar to 25X-NBOMe compounds—25B-NBOH, 25C-NBOH, 25E-NBOH, and 25I-NBOH—were tested in mice and rats. All four decreased spontaneous locomotor activity in mice, with effects similar in magnitude and potency to the hallucinogen DOM but less potent than 25X-NBOMe compounds. In rats trained to discriminate DOM, 25B-NBOH, 25C-NBOH, and 25E-NBOH fully substituted for DOM, indicating they produce similar psychoactive effects, while 25I-NBOH failed to fully substitute even at doses that suppressed responding. The findings suggest three of the four compounds are likely to be used recreationally as hallucinogens, whereas 25I-NBOH may have lower abuse liability.