Our Love Affair with Drugs
October 1, 2020
Jerrold C Winter
Abstract As these words are written, the chemical we will call MDMA is a Schedule I drug. This means that MDMA (a) has no currently accepted medical use, (b) no currently accepted safety even under medical supervision, and (c) has a high potential for abuse. On the other hand, there are those who see great therapeutic potential in MDMA, and the Food and Drug Administration (FDA) has designated...
October 1, 2020
Jerrold C Winter
Abstract There are about 400,000 species of plants in this world. Only a small fraction, perhaps 100 in number, contain hallucinogenic chemicals. Nearly a century ago, Lewis Lewin, professor of pharmacology at the University of Berlin, in speaking of drugs he called phantasticants, said “The passionate desire which … leads man to flee from the monotony of daily life … has made him discover...
Pharmacology, biochemistry, and behavior
September 1, 2011
Jerrold C Winter, D J Amorosi, Kenner C Rice et al.
10 citations
In previous studies we have observed that, in comparison with wild type mice, Tg-CYP2D6 mice have increased serum levels of bufotenine [5-hydroxy-N,N-dimethyltryptamine] following the administration of 5-MeO-DMT. Furthermore, following the injection of 5-MeO-DMT, harmaline was observed to increase serum levels of bufotenine and 5-MeO-DMT in both wild-type and Tg-CYP2D6 mice. In the present...
Current Drug Metabolism
October 1, 2010
Hong-Wu Shen, Xi-Ling Jiang, Jerrold C Winter et al.
171 citations
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination...
Psychopharmacology
April 2009
J C Winter
Although man's first encounters with hallucinogens predate written history, it was not until the rise of the sister disciplines of organic chemistry and pharmacology in the nineteenth century that scientific studies became possible. Mescaline was the first to be isolated and its chemical structure determined. Since then, additional drugs have been recovered from their natural sources and...
Pharmacology, biochemistry, and behavior
January 2008
C M Krall, J B Richards, R A Rabin et al.
Based upon extensive studies in the rat, it has been suggested that stimulus control by LSD is mediated by 5-HT2A receptors, with serotonergic receptors of the 5-HT1A and 5-HT2C subtypes playing modulatory roles. In genetically modified mice lacking the serotonin transporter (SERT), 5-HT2A receptor density is decreased and, at a functional level, the head-twitch response following the...
Pharmacology, biochemistry, and behavior
January 2008
William E Fantegrossi, Chad J Reissig, Elyse B Katz et al.
N,N-dipropyltryptamine (DPT) is a synthetic tryptamine hallucinogen which has been used psychotherapeutically in humans, but has been studied preclinically only rarely. In the present studies, DPT was tested in a drug-elicited head-twitch assay in mice, and in rats trained to discriminate lysergic acid diethylamide (LSD), N,N-dimethyl-4-phosphoryloxytryptamine (psilocybin), or...
Pharmacology, biochemistry, and behavior
January 2008
J C Winter
It has been observed that agents with agonist activity at 5-HT2A receptors prevent neurotoxicity induced by the non-competitive NMDA antagonist, dizocilpine (MK-801). Subsequent behavioral studies reported complete antagonism by LSD and DOM of the stimulus effects of the related NMDA antagonist, phencyclidine [PCP]. The present study sought to extend those observations to include other...
Pharmacology, biochemistry, and behavior
October 1, 2007
Jerrold C Winter, K C Rice, D J Amorosi et al.
73 citations
Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following...
Pharmacology, biochemistry, and behavior
2006
William E Fantegrossi, A W Harrington, C L Kiessel et al.
144 citations
Few studies have examined the effects of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) in vivo. In these studies, 5-MeO-DIPT was tested in a drug-elicited head twitch assay in mice where it was compared to the structurally similar hallucinogen N,N-dimethyltryptamine (N,N-DMT) and challenged with the selective serotonin (5-HT)2A antagonist M100907, and in a lysergic acid diethylamide (LSD)...
Psychopharmacology
October 2005
C J Reissig, J R Eckler, R A Rabin et al.
It has been suggested that the 5-HT1A receptor plays a significant modulatory role in the stimulus effects of the indoleamine hallucinogen lysergic acid diethylamide (LSD). The present study sought to characterize the effects of several compounds with known affinity for the 5-HT1A receptor on the discriminative stimulus effects of LSD. Twelve male Fischer 344 rats were trained in a two-lever,...
Psychopharmacology
September 1, 2005
William E Fantegrossi, Andrew W Harrington, Justin R Eckler et al.
72 citations
Few studies have examined the effects of 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) in vivo. 2C-T-7 was tested in a drug-elicited head twitch assay in mice and in several drug discrimination assays in rats; 2C-T-7 was compared to the phenylisopropylamine hallucinogen R(-)-1-(2,5-dimethoxy-4-methylphenyl)-2aminopropane (DOM) in both assays, with or without pretreatment with the...
Pharmacology, biochemistry, and behavior
August 2005
J C Winter, A K Kieres, M D Zimmerman et al.
Drug-induced stimulus control has proven to be a powerful tool for the assessment of a wide range of psychoactive drugs. Although a variety of species has been employed, the majority of studies have been in the rat. However, with the development of techniques which permit the genetic modification of mice, the latter species has taken on new importance. Lysergic acid diethylamide [LSD], the...
Pharmacology, biochemistry, and behavior
July 2005
J C Winter, J R Eckler, K C Rice et al.
Previous investigations in our laboratory have found that the stimulus effects of the hallucinogenic serotonergic agonists DOM and LSD are potentiated by phencyclidine [PCP], a non-competitive NMDA antagonist. Also suggestive of behaviorally significant serotonergic/glutamatergic interactions is our finding that stimulus control by both PCP and LSD is partially antagonized by the mGlu2/3...
Pharmacology, biochemistry, and behavior
September 2004
J R Eckler, C J Reissig, R A Rabin et al.
Previous studies conducted in our laboratory have shown that acute administration of the selective serotonin re-uptake inhibitor (SSRI), citalopram, potentiates the stimulus effects of the phenethylamine hallucinogen [-]-2,5-dimethoxy-4-methylamphetamine (DOM) in the rat while neither substituting for the DOM stimulus when administered alone nor altering brain levels of DOM. The present...
Brain Research
August 27, 2004
John W. Muschamp, Meredith J. Regina, Elaine M. Hull et al.
116 citations
The ability of hallucinogens to increase extracellular glutamate in the prefrontal cortex (PFC) was assessed by in vivo microdialysis. The hallucinogen lysergic acid diethylamide (LSD; 0.1 mg/kg, i.p.) caused a time-dependent increase in PFC glutamate that was blocked by the 5-HT(2A) antagonist M100907 (0.05 mg/kg, i.p.). Similarly, the 5-HT(2A/C) agonist [-]-2,5-dimethoxy-4-methylamphetamine...
Neuropharmacology
December 2003
Meredith J Regina, Jerrold C Winter, Richard A Rabin
Elucidating the mechanisms of action of hallucinogens has become an increasingly important area of research as their abuse has grown in recent years. Although serotonin receptors appear to play a role in the behavioral effects of the phenethylamine and indoleamine hallucinogens, the signaling pathways activated by these agents are unclear. Here it is shown that administration of serotonin...
Pharmacology, biochemistry, and behavior
July 2003
J R Eckler, J Chang-Fong, R A Rabin et al.
The present investigation was undertaken to test the hypothesis that known metabolites of the phenylethylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) are pharmacologically active. This hypothesis was tested by evaluating the ability of racemic DOM metabolites 2-O-desmethyl DOM (2-DM-DOM) and 5-O-desmethyl DOM (5-DM-DOM) to substitute for the stimulus properties of...
Pharmacology, biochemistry, and behavior
May 2003
J R Eckler, R A Rabin, J C Winter
Nefazodone is presently marketed as an antidepressant that inhibits both serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine reuptake while antagonizing pirenpirone (5-HT2) receptors. This 5-HT receptor type is believed to play a prominent role in the underlying mechanism of action of serotonergic hallucinogens. Antidepressant medications now represent the most commonly prescribed...
Pharmacology, biochemistry, and behavior
February 2003
Mireille M Doat, Richard A Rabin, Jerrold C Winter
Despite the plausible assumption that the effects of hallucinogens predominantly arise in the central nervous system, most studies of these drugs in intact subjects have been conducted following systemic administration. The objective of the present investigation was to characterize the stimulus effects of (-)2,5-dimethoxy-4-methylamphetamine ((-)-DOM) following intracerebroventricular...
Pharmacology, biochemistry, and behavior
December 2002
J C Winter, J R Eckler, M M Doat et al.
Previous reports from our laboratory have provided evidence that acute, i.e., concurrent, treatment with selective serotonin reuptake inhibitors (SSRIs) augments the stimulus effects of indoleamine and phenethylamine hallucinogens in the rat. In the present investigation, the acute effects of fluoxetine and citalopram on stimulus control induced by (-)-2,5-dimethoxy-4-methylamphetamine (DOM)...
Pharmacology, biochemistry, and behavior
May 2002
Richard A Rabin, Meredith Regina, Mireille Doat et al.
The role of 5-HT2A-mediated stimulation of phosphoinositide hydrolysis in the discriminative effects of hallucinogens was investigated in PC12 cells stably expressing the rat 5-HT2A receptor (PC12-5-HT2A cells). The hallucinogenic compounds, D-lysergic acid diethylamide (LSD), (-)2,5-dimethoxy-4-methylamphetamine (DOM), psilocybin, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine...
The Alkaloids. Chemistry and biology
2001
Scott Helsley, R A Rabin, Jerrold C Winter
4 citations
The results of the studies described here support the hypothesis that ibogaine produces its effects via selective interactions with multiple receptors. It appears that 5-HT2A, 5-HT2C, and sigma 2 receptors are involved in mediating the stimulus effects of ibogaine. In addition, opiate receptors may also be involved. In contrast, sigma 1, PCP/MK-801, 5-HT3, and 5-HT1A receptors do not appear to...
Journal of pharmacological and toxicological methods
2001
J R Eckler, H Greizerstein, R A Rabin et al.
Indolamine and phenethylamine hallucinogens are drugs of abuse and, as well, mimic some aspects of idiopathic psychosis. To assist in investigating the mechanisms of action of (-)2,5-dimethoxy4-methylamphetamine ([-]-DOM), a member of the phenethylamine class of serotonergic hallucinogens, a sensitive and precise method for determining its levels in the brain tissue is required. We now describe...
Life Sciences
December 8, 2000
Jerrold C Winter, M Doat, R A Rabin
The present investigation examined the interaction between 2,5-dimethoxy-4-methylamphetamine [DOM] and non-competitive NMDA antagonists in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with phencyclidine [PCP] at a dose of 3 mg/kg shifted the DOM dose-response relationship to the left. When a fixed dose of DOM [0.1 mg/kg] which by itself...