Skip to main content
SpringerLink
Log in

Comparison of the discriminative stimulus effects of dimethyltryptamine with different classes of psychoactive compounds in rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

There has been increased recreational use of dimethyltryptamine (DMT), but little is known of its discriminative stimulus effects.

Objectives

The present study assessed the similarity of the discriminative stimulus effects of DMT to other types of hallucinogens and to psychostimulants.

Methods

Rats were trained to discriminate DMT from saline. To test the similarity of DMT to known hallucinogens, the ability of (+)-lysergic acid diethylamide (LSD), (−)-2,5-dimethoxy-4-methylamphetamine (DOM), (+)-methamphetamine, or (±)3,4-methylenedioxymethyl amphetamine (MDMA) to substitute in DMT-trained rats was tested. The ability of DMT to substitute in rats trained to discriminate each of these compounds was also tested. To assess the degree of similarity in discriminative stimulus effects, each of the compounds was tested for substitution in all of the other training groups.

Results

LSD, DOM, and MDMA all fully substituted in DMT-trained rats, whereas DMT fully substituted only in DOM-trained rats. Full cross-substitution occurred between DMT and DOM, LSD and DOM, and (+)-methamphetamine and MDMA. MDMA fully substituted for (+)-methamphetamine, DOM, and DMT, but only partially for LSD. In MDMA-trained rats, LSD and (+)-methamphetamine fully substituted, whereas DMT and DOM did not fully substitute. No cross-substitution was evident between (+)-methamphetamine and DMT, LSD, or DOM.

Conclusions

DMT produces discriminative stimulus effects most similar to those of DOM, with some similarity to the discriminative stimulus effects of LSD and MDMA. Like DOM and LSD, DMT seems to produce predominately hallucinogenic-like discriminative stimulus effects and minimal psychostimulant effects, in contrast to MDMA which produced hallucinogen- and psychostimulant-like effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Adams LM, Geyer MA (1985) Effects of DOM and DMT in a proposed animal model of hallucinogenic activity. Prog Neuropsychopharmacol Biol Psychiatry 9:121–132

    Article  PubMed  CAS  Google Scholar 

  • Appel JB, West WB, Rolandi WG, Alici T, Pechersky K (1999) Increasing the selectivity of drug discrimination procedures. Pharmacol Biochem Behav 64:353–358

    Article  PubMed  CAS  Google Scholar 

  • Baker LE, Broadbent J, Michael EK, Matthews PK, Metosh CA, Saunders RB, West WB, Appel JB (1995) Assessment of the discriminative stimulus effects of the optical isomers of ecstasy (3, 4-methylenedioxymethamphetamine; MDMA). Behav Pharmacol 6:263–275

    Article  PubMed  CAS  Google Scholar 

  • Balster RL (1991) Drug abuse potential evaluation in animals. Brit J Addict 86:1549–1558

    Article  CAS  Google Scholar 

  • Barker SA, Monti JA, Christian ST (1981) N,N-dimethyltryptamine: an endogenous hallucinogen. Int Rev Neurobiol: 83-110

  • Broadbent J, Appel JB, Michael EK, Ricker JH (1992) Discriminative stimulus effects of the optical isomers of 3,4-methylenedioxyamphetamine (MDA). Behav Pharmacol 3:443–454

    Article  PubMed  CAS  Google Scholar 

  • Callahan PM, Appel JB (1988) Differences in the stimulus properties of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine in animals trained to discriminate hallucinogens from saline. J Pharmacol Exp Ther 246:866–870

    PubMed  CAS  Google Scholar 

  • Cooper SG, Schiff SR, Bridger WH (1981) Tolerance to behavioral effects of N,N-dimethyltryptamine in mice. Biol Psychiatry 16:864–867

    Google Scholar 

  • Doat MM, Rabin RA, Winter JC (2003) Characterization of the discriminative stimulus properties of centrally administered (−)-DOM and LSD. Pharmacol Biochem Behav 74:713–721

    Article  PubMed  CAS  Google Scholar 

  • File SE (1977) Effects of N,N-dimethyltryptamine on behavioural habituation in the rat. Pharmacol Biochem Behav 6:163–168

    Article  PubMed  CAS  Google Scholar 

  • Fiorella D, Palumbo PA, Rabin RA, Winter JC (1995) The time-dependent stimulus effects of R(−)-2, 5-dimethoxy-4-methamphetamine (DOM): implications for drug-induced stimulus control as a method for the study of hallucinogenic agents. Psychopharmacology 119:239–245

    Article  PubMed  CAS  Google Scholar 

  • Gable RS (2007) Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids. Addiction 102:24–34

    Article  PubMed  Google Scholar 

  • Gillin JC, Kaplan J, Stillman R, Wyatt RJ (1976) The psychedelic model of schizophrenia: the case of N,N-dimethyltryptamine. Am J Psychiatry 133:203–208

    PubMed  CAS  Google Scholar 

  • Glennon RA (1986) Discriminative stimulus properties of phenylisopropylamine derivatives. Drug Alc Depend 17:119–134

    Article  CAS  Google Scholar 

  • Glennon RA (1999) Arylalkylamine drugs of abuse: an overview of drug discrimination studies. Pharmacol Biochem Behav 64:251–256

    Article  PubMed  CAS  Google Scholar 

  • Glennon RA, Young R, Rosecrans JA, Kallman MJ (1980) Hallucinogenic agents as discriminative stimuli: a correlation with serotonin receptor affinities. Psychopharmacology 68:155–158

    Article  PubMed  CAS  Google Scholar 

  • Glennon RA, Young R, Rosecrans JA, Anderson GM (1982) Discriminative stimulus properties of MDA analogs. Biol Psychiatry 17:807–814

    PubMed  CAS  Google Scholar 

  • Glennon RA, Young R, Jacyno JM, Slusher M, Rosecrans JA (1983) DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines. Eur J Pharmacol 86:453–459

    Article  PubMed  CAS  Google Scholar 

  • Grant KA (1999) Strategies for understanding the pharmacological effects of ethanol with drug discrimination procedures. Pharmacol Biochem Behav 64:261–267

    Article  PubMed  CAS  Google Scholar 

  • Halpern JH (2004) Hallucinogens and dissociative agents naturally growing in the United States. Pharmacol Ther 102:131–138

    Article  PubMed  CAS  Google Scholar 

  • Hamik A, Peroutka SJ (1989) 1-(m-chlorophenyl) piperazine (mCPP) interactions with neurotransmitter receptors in the human brain. Biol Psychiatry 25:569–575

    Article  PubMed  CAS  Google Scholar 

  • Helsley S, Fiorella D, Rabin RA, Winter JC (1998) A comparison of N,N-dimethyltryptamine, harmaline, and selected congeners in rats trained with LSD as a discriminative stimulus. Prog Neuropsychopharmacol Biol Psychiatry 22:649–663

    Article  PubMed  CAS  Google Scholar 

  • Heuring RE, Peroutka SJ (1987) Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes. J Neurosci 7:894–903

    PubMed  CAS  Google Scholar 

  • Jarbe TUC (1980) LSD-25 as a discriminative stimulus for response selection by pigeons. Pharmacol Biochem Behav 13:549–554

    Article  PubMed  CAS  Google Scholar 

  • Jenner P, Marsden CD, Thanki CM (1980) Behavioural changes induced by N,N-dimethyl-tryptamine in rodents. Br J Pharmacol 69:69–80

    PubMed  CAS  Google Scholar 

  • Khorana N, Pullogurla MR, Young R, Glennon RA (2004) Comparison of the discriminative stimulus effects of 3, 4-methylenedioxymethamphetamine (MDMA) and cocaine: asymmetric generalization. Drug Alc Depend 74:281–287

    Article  CAS  Google Scholar 

  • Kovacic B, Domino EF (1976) Tolerance and limited cross-tolerance to the effects of N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) on food-rewarded bar pressing in the rat. J Pharmacol Exp Ther 197:495–502

    PubMed  CAS  Google Scholar 

  • Kovacic B, Wang Lu LJ, Ruffing D, Domino EF (1978) Interactions of partial LSD analogs with behavioral disrupting effects of LSD and DMT in the rat. Eur J Pharmacol 47:37–44

    Article  PubMed  CAS  Google Scholar 

  • Kueh D, Baker LE (2007) Reinforcement schedule effects in rats trained to discriminate 3, 4-methylenedioxymethamphetamine (MDMA) or cocaine. Psychopharmacology 189:447–457

    Article  PubMed  CAS  Google Scholar 

  • Lyon RA, Titeler M, Seggel MR, Glennon RA (1988) Indolealkylamine analogs share 5-HT2 binding characteristics with phenylalkylamine hallucinogens. Eur J Pharmacol 145:291–297

    Article  PubMed  CAS  Google Scholar 

  • McKenna DJ (2004) Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacol Ther 102:111–129

    Article  PubMed  CAS  Google Scholar 

  • McKenna DJ, Peroutka SJ (1989) Differentiation of 5-hydroxytryptamine2 receptor subtypes using 125I-R-(−) 2, 5-dimethoxy-4-iodo-phenylisopropylamine and 3H-ketanserin. J Neurosci 9:3482–3490

    PubMed  CAS  Google Scholar 

  • McKenna DJ, Towers GH, Abbott F (1984) Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca. J Ethnopharmacol 10:195–223

    Article  PubMed  CAS  Google Scholar 

  • National Research Council (2003) Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research. The National Academies Press, The National Academies Press

  • Nichols DE (2004) Hallucinogens. Pharmacol Ther 101:131–181

    Article  PubMed  CAS  Google Scholar 

  • Oberlender R, Nichols DE (1988) Drug discrimination studies with MDMA and amphetamine. Psychopharmacology 95:71–76

    Article  PubMed  CAS  Google Scholar 

  • Ott J (1999) Pharmahuasca: human pharmacology of oral DMT plus harmine. J Psychoactive Drugs 31:171–177

    PubMed  CAS  Google Scholar 

  • Pierce PA, Peroutka SJ (1989) Hallucinogenic drug interactions with neurotransmitter receptor binding sites in human cortex. Psychopharmacology 97:118–122

    Article  PubMed  CAS  Google Scholar 

  • Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ (2003) Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics. J Pharmacol Exp Ther 306:73–83

    Article  PubMed  CAS  Google Scholar 

  • Ruffing DM, Domino EF (1983) Interaction of synthetic opioid metenkephalin peptide analogs, Lilly 127623 and FK 33–824 with indole hallucinogens: antagonism of N,N-dimethyltryptamine- and LSD-induced disruption of food-rewarded bar pressing behavior in the rat. Psychopharmacology 80:315–318

    Article  PubMed  CAS  Google Scholar 

  • Sadzot B, Baraban JM, Glennon RA, Lyon RA, Leonhardt S, Jan CR, Titeler M (1989) Hallucinogenic drug interactions at human brain 5-HT2 receptors: implications for treating LSD-induced hallucinogenesis. Psychopharmacology 98:495–499

    Article  PubMed  CAS  Google Scholar 

  • Sbordone RJ, Wingard JA, Gorelick DA, Elliott ML (1979) Severe aggression in rats induced by mescaline but not other hallucinogens. Psychopharmacology (Berl) 66:275–280

    Article  CAS  Google Scholar 

  • Schechter MD (1998) MDMA-like stimulus effects of hallucinogens in male Fawn-Hooded rats. Pharmacol Biochem Behav 59:265–270

    Article  PubMed  CAS  Google Scholar 

  • Schoenfeld RI (1976) Lysergic acid diethylamide- and mescaline-induced attenuation of the effect of punishment in the rat. Science 192:801–803

    Article  PubMed  CAS  Google Scholar 

  • Smith RL, Canton H, Barrett RJ, Sanders-Bush E (1998) Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors. Pharmacol Biochem Behav 61:323–330

    Article  PubMed  CAS  Google Scholar 

  • Stoff DM, Moja EA, Gillin JC, Wyatt RJ (1977) Dose response and time course effects of N,N-dimethyltryptamine on disruption of rat shuttlebox avoidance. Biol Psychiatry 12:339–346

    PubMed  CAS  Google Scholar 

  • Stolerman IP (1993) Drug discrimination. In: Van Haaren F (ed) Methods in Behavioral Pharmacology. Elsevier, Amsterdam, pp 217–243

    Google Scholar 

  • Strassman RJ, Qualls CR, Uhlenhuth EH, Kellner R (1994) Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry 51:98–108

    PubMed  CAS  Google Scholar 

  • Strassman RJ, Qualls CR, Berg LM (1996) Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans. Biol Psychiatry 39:784–795

    Article  PubMed  CAS  Google Scholar 

  • Szara S, Rockland LH, Rosenthal D, Handlon JH (1966) Psychological effects and metabolism of N,N-diethyltryptamine in man. Arch Gen Psychiatry 15:320–329

    PubMed  CAS  Google Scholar 

  • Walters JK, Sheard MH, Davis M (1978) Effects of N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on shock elicited fighting in rats. Pharmacol Biochem Behav 9:87–90

    Article  PubMed  CAS  Google Scholar 

  • West WB, Lou A, Pechersky K, Chachich ME, Appel JB (2000) Antagonism of a PCP drug discrimination by hallucinogens and related drugs. Neuropsychopharmacology 22:618–625

    Article  PubMed  CAS  Google Scholar 

  • Winter JC (2009) Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines. Psychopharmacology in press

  • Winter JC, Rice KC, Amorosi DJ, Rabin RA (2007) Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav 87:472–480

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Funding was provided by the Addiction Treatment Discovery Program of the National Institute on Drug Abuse (NIH N01DA-2-8822). Program staff were involved in selection of compounds and test parameters. The ATDP had no further role in study design; the collection, analysis and interpretation of data; or the writing of the report. They have granted permission for the submission of this data for publication.

Author information

Authors and Affiliations

  1. Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, 76107-2699, USA

    Michael B. Gatch, Margaret A. Rutledge, Theresa Carbonaro & Michael J. Forster

Authors
  1. Michael B. Gatch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Margaret A. Rutledge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Theresa Carbonaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael J. Forster
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael B. Gatch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gatch, M.B., Rutledge, M.A., Carbonaro, T. et al. Comparison of the discriminative stimulus effects of dimethyltryptamine with different classes of psychoactive compounds in rats. Psychopharmacology 204, 715–724 (2009). https://doi.org/10.1007/s00213-009-1501-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-009-1501-z

Keywords

Search

Navigation