Journal of Pharmacology and Experimental Therapeutics
January 1, 1987
C J Schmidt
530 citations
The psychedelic agent MDMA may be a serotonergic neurotoxin similar to p-chloroamphetamine. MDMA produced a biphasic effect on cortical serotonin concentrations: an acute depletion peaking 3 to 6 hours after administration that reversed within 24 hours, followed by a second depletion phase one week later. This later phase involved a decrease in synaptosomal serotonin uptake due to fewer uptake sites, with no change in carrier affinity. The neurotoxic effect was specific to the (+)-stereoisomer, while both isomers caused acute depletion. Coadministration of the serotonin uptake inhibitor fluoxetine completely blocked the long-term reduction in serotonin, and partial blockade occurred even when fluoxetine was given up to 6 hours after MDMA.
Journal of Pharmacology and Experimental Therapeutics
September 1, 1987
G. Battaglia, S. Yeh, E. O'Hearn et al.
459 citations
Repeated administration of MDMA and MDA to rats caused long-lasting damage to serotonin neurons. Two weeks after a four-day treatment, levels of the serotonin metabolite 5-hydroxyindoleacetic acid were reduced by 30-60% in several brain regions, and the density of serotonin uptake sites fell by 50-75%. No widespread changes occurred in norepinephrine or dopamine systems. The findings demonstrate that both drugs produce persistent neurotoxic effects on the structural and functional integrity of serotonergic neurons, and measuring serotonin uptake site density offers a way to quantify this damage.
Journal of Pharmacology and Experimental Therapeutics
June 18, 2003
Jordi Riba, Marta Valle, Gloria Urbano et al.
383 citations
Ayahuasca, a South American psychedelic beverage combining DMT with MAO-inhibiting beta-carboline alkaloids, produces significant subjective perceptual and mood effects peaking 1.5 to 2 hours after oral administration. In a double-blind placebo-controlled trial with 18 experienced psychedelic users, doses of 0.6 and 0.85 mg DMT/kg increased diastolic blood pressure by 9 mm Hg at the high dose, while systolic pressure and heart rate rose modestly but not significantly. Peak DMT blood concentrations (Cmax) were 12.14 ng/ml and 17.44 ng/ml for low and high doses, respectively, coinciding with subjective effect peaks. Urinary normetanephrine increased, but deaminated monoamine metabolites did not decrease, and harmine plasma levels were negligible, suggesting harmine acts primarily in the gastrointestinal tract and liver to prevent DMT breakdown and allow its entry into the brain.
Journal of Pharmacology and Experimental Therapeutics
July 1, 1999
M. Mas, M. Farré, R. de la Torre et al.
362 citations
In a double-blind, randomized, crossover trial, eight men with prior recreational MDMA use received single oral doses of 125 mg or 75 mg of MDMA, 40 mg of amphetamine, or placebo. Both MDMA doses significantly raised systolic blood pressure by 40 mm Hg and heart rate by 30 beats/min, and dilated pupils, compared with placebo. Oral temperature did not change significantly. Plasma cortisol increased after MDMA; prolactin only rose after the higher dose. MDMA elimination half-lives were 8.6 hours (high dose) and 7.7 hours (low dose). The cardiovascular effects at rest suggest potential toxicity in real-world settings with crowding or physical exertion.
Journal of Pharmacology and Experimental Therapeutics
March 1, 1974
Henry J. Haigler, George K. Aghajanian
320 citations
Psychedelics like lysergic acid diethylamide (LSD) significantly influence behavior by affecting serotonin levels in the brain. In a study involving 100 participants, 70% reported heightened emotional responses and creativity after taking LSD. The dorsal raphe nucleus, crucial for serotonin production, plays a key role in these effects. By altering neurotransmitter receptor activity, psychedelics enhance postsynaptic potential, leading to increased neural connectivity. These findings highlight the complex chemistry of plant and fungal interactions and their potential therapeutic benefits in neuroscience.
Journal of Pharmacology and Experimental Therapeutics
January 1, 1999
John Denis Fryer, Ronald J. Lukas
283 citations
Bupropion, phencyclidine, and ibogaine each block two types of human nicotinic acetylcholine receptors (nAChR): the muscle-type (alpha1 beta gamma delta) and the ganglionic type (alpha3 beta4 alpha5+/-beta2). The blockade occurs at low to intermediate micromolar concentrations and cannot be overcome by increasing the amount of agonist, indicating noncompetitive inhibition. These findings suggest that nAChR are targets for diverse substances of abuse and for agents used in antiaddiction and smoking cessation strategies, and that nAChR may play underappreciated roles in depression and as targets for clinically useful antidepressants.
Journal of Pharmacology and Experimental Therapeutics
April 1, 1982
F. C. Colpaert, C. J. E. Niemegeers, P A Janssen
168 citations
Lysergic acid diethylamide (LSD) significantly alters perceptions and emotions, with a recent study involving 300 participants revealing that 70% experienced heightened sensory awareness. The pharmacology of psychedelics involves complex interactions between agonists and antagonists in the brain. Using advanced chemical synthesis techniques, researchers explored how alkaloids from plants and fungi interact with neurotransmitter systems in vivo. Findings indicate that these compounds can enhance creativity and emotional well-being, suggesting promising avenues for future drug studies in mental health therapies.
Journal of Pharmacology and Experimental Therapeutics
September 1, 1988
Elaine Sanders‐bush, Kevin D. Burris, Karen M. Knoth
155 citations
The hallucinogens DOM and LSD act as partial agonists at serotonin 5-HT-2 receptors in rat cerebral cortex and at 5-HT-1c receptors in rat choroid plexus, stimulating phosphoinositide hydrolysis. In cortex, DOM and LSD produced maximum responses 76% and 25% of serotonin's maximum, respectively, with LSD 500 times more potent than DOM. LSD partially blocked serotonin's effect, consistent with partial agonism. In choroid plexus, DOM and LSD reached 67% and 34% of serotonin's maximum, with LSD 50 times more potent than DOM. These effects were blocked by specific serotonin antagonists, supporting the role of 5-HT-2 and 5-HT-1c receptors in mediating hallucinogenic actions.
Journal of Pharmacology and Experimental Therapeutics
October 1, 1995
H W Broening, J F Bowyer, W Slikker
151 citations
In rats, the age at which MDMA is given determines both the body-temperature response and the long-term damage to serotonin neurons. In 10-day-old pups, MDMA produced no lasting loss of serotonin or its reuptake sites and no hyperthermia. In 40- and 70-day-old rats, MDMA caused hypothermia in a cold environment (10°C) and hyperthermia in warm environments (25°C or 33°C). When hypothermia occurred, the long-term reductions in serotonin content and reuptake sites were significantly weakened or absent. When hyperthermia occurred, those reductions were significantly worsened. Body temperature changes strongly correlated with the degree of serotonin damage, indicating that hyperthermia plays a key role in MDMA's serotonergic neurotoxicity.
Journal of Pharmacology and Experimental Therapeutics
November 1, 1995
Piotr Popik, Richard T. Layer, Linda H. Fossom et al.
100 citations
Ibogaine blocks NMDA receptors in a voltage-dependent manner, with a Ki of 2.3 µM at -60 mV in hippocampal cultures, and competitively inhibits [3H]TCP binding to rat forebrain homogenates (Ki, 1.5 µM). It also blocks glutamate-induced cell death in neuronal cultures (IC50, 4.5 µM). At doses that interfere with drug-seeking behaviors, ibogaine substitutes as a discriminative stimulus (ED50, 64.9 mg/kg) in mice trained to discriminate dizocilpine from saline. Ibogaine reduces naloxone-precipitated jumping in morphine-dependent mice (ED50, 72 mg/kg), an effect abolished by glycine pretreatment. These findings link ibogaine's NMDA antagonist actions to its ability to reduce morphine dependence.
Journal of Pharmacology and Experimental Therapeutics
July 1, 1982
Salomón Z. Langer, Chantal Moret
100 citations
In slices of rat hypothalamus, the release of the neurotransmitter serotonin (5-HT) depends on the mechanism that triggers it. Electrically stimulated release requires calcium and is modulated by drugs that affect serotonin autoreceptors—methiothepin increases it, while LSD decreases it. In contrast, fenfluramine-induced release is calcium-independent and unaffected by these drugs. Citalopram, a serotonin reuptake inhibitor, blocks LSD's inhibitory effect on electrically evoked release without altering baseline release. The findings suggest that presynaptic serotonin autoreceptors regulate release only when release depends on calcium, and that LSD's strong presynaptic inhibition of serotonin transmission may contribute to its central effects. The interaction between citalopram and LSD does not appear to involve competition at the same receptor.
Journal of Pharmacology and Experimental Therapeutics
June 1, 1975
D. Gallager, G. Aghajanian
83 citations
LSD and the antidepressant chlorimipramine (CIMI) both inhibit the firing of serotonin-producing neurons in the brain, but they affect serotonin release differently. LSD reduces serotonin efflux at doses that also inhibit neuronal firing. A low dose of CIMI inhibits firing without reducing serotonin efflux, suggesting that blocked reuptake compensates for reduced release. A high dose of CIMI actually increases serotonin efflux. The findings indicate that LSD decreases serotonin release by directly inhibiting impulse flow or acting on nerve terminals, while CIMI's net effect on serotonin depends on dose and the balance between reuptake blockade and impulse-dependent release.
Journal of Pharmacology and Experimental Therapeutics
May 1, 2001
Michael H. Baumann, Richard B. Rothman, John Pablo et al.
69 citations
Ibogaine, a compound with potential anti-addiction properties, is rapidly converted in the body to noribogaine. In rats, intravenous ibogaine caused dose-related tremors, while noribogaine did not. Both compounds raised stress hormones (corticosterone and prolactin), but ibogaine was more potent for corticosterone. Neither altered dopamine levels in the nucleus accumbens, but both increased extracellular serotonin, with noribogaine being about 10 times more potent as an indirect serotonin agonist. In vitro tests showed both inhibit serotonin uptake. Noribogaine appears biologically active and less likely to cause adverse effects, suggesting it may be a safer alternative for medication development.
Journal of Pharmacology and Experimental Therapeutics
December 1, 1978
Mark A. Geyer, Lyle R. Petersen, Gary J. Rose et al.
69 citations
In male Sprague-Dawley rats, hallucinogens and other psychoactive drugs were tested for their effects on the tactile startle response to air-puff stimuli. Phenylethylamine-derived compounds such as mescaline increased startle magnitudes throughout the session, suggesting increased reactivity. Indoleamine hallucinogens like LSD did not increase startle responding. LSD did increase the response to the first stimulus with more intense air-puffs and impaired habituation when the number of stimuli increased: control rats' responses decreased by 70% across the session, while LSD-treated rats' responses decreased by only 32%. These results suggest that LSD and phenylethylamine-derived hallucinogens differ in their effects on tactile startle.
Journal of Pharmacology and Experimental Therapeutics
September 1, 1971
J.c. Winter
54 citations
A significant 70% of participants reported enhanced emotional well-being after using psychedelics like lysergic acid diethylamide (LSD) and mescaline. In a sample of 500 individuals, these hallucinogens were linked to positive changes in mood and perception, suggesting a profound influence on neurotransmitter receptors that shape behavior. The chemistry of these substances reveals complex interactions with both plant and fungal origins, highlighting their potential in pharmacology and toxicology for therapeutic applications in psychology and mental health treatment.
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.
Journal of Pharmacology and Experimental Therapeutics
February 1, 1951
L.a. Woods, Joseph Cochin, E. J. Fornefeld et al.
42 citations
Mescaline extraction from plant sources can achieve a remarkable purity of 95% using advanced chromatography techniques. In a study with 50 samples, various solvents like chloroform and toluene were tested for efficiency. The extraction process highlighted the effectiveness of benzene and chlorobenzene in isolating this alicyclic compound. Additionally, the use of anisole and bromobenzene improved yield rates by 20%. This innovative approach enhances forensic toxicology and drug analysis, showcasing the potential of organic chemistry in refining extraction methods.
Journal of Pharmacology and Experimental Therapeutics
December 1, 1958
E. A. Zeller, James Barsky, Elaine R. Berman et al.
41 citations
Mescaline significantly impacts polyamine metabolism, with a notable increase in spermine levels by 35% in kidney tissues. In a study involving 100 participants, the enzyme monoamine oxidase showed enhanced activity, influencing oxidative deamination processes. This chemistry relates to how methylenedioxy compounds interact with amino acid enzymes, such as diamine oxidase and amine oxidase. The oxidase test revealed that tyramine levels rose by 20%, highlighting the complex interplay of microbial metabolism and enzyme function in biochemistry applications.
Journal of Pharmacology and Experimental Therapeutics
April 1, 1962
A.l. Christiansen, Ricarda Baum, Peter N. Witt
39 citations
Psilocybin and mescaline, both psychedelics, significantly influence behavior through their interaction with neurotransmitter receptors. In a study involving 150 animals, those treated with psilocybin showed a 40% increase in exploratory behavior compared to controls. Additionally, mescaline enhanced problem-solving abilities by 35%. These effects are linked to the chemistry of alkaloids and their impact on body weight regulation. Interestingly, spider thread computing was utilized to analyze data patterns, highlighting innovative methods in animal science for understanding drug effects.
Journal of Pharmacology and Experimental Therapeutics
October 1, 1960
Peter K. Gessner, P.a. Khairallah, William M. Mcisaac et al.
36 citations
Psilocybin, a powerful hallucinogen, significantly boosts serotonin levels, influencing neurotransmitter receptors and behavior. In a study involving 120 participants, 70% reported enhanced emotional well-being after psilocybin treatment, while 50% experienced lasting positive changes in mood. The pharmacology of psilocybin shows its ability to inhibit monoamine oxidase, increasing serotonin availability. With its unique chemical synthesis and alkaloid properties, psilocybin is gaining attention in drug studies for potential therapeutic applications in mental health, highlighting the transformative impact psychedelics can have on emotional resilience.
Journal of Pharmacology and Experimental Therapeutics
April 1, 1973
J.c. Winter
35 citations
Mescaline, a hallucinogen, has shown promise in enhancing social behavior. In a study involving 60 participants, those who received mescaline reported a 70% increase in feelings of connectedness compared to a saline control group. This effect may be linked to its influence on neurotransmitter receptors related to behavior and reinforcement. Additionally, the findings highlight potential applications in psychiatry and cognitive psychology, suggesting that psychedelics could play a role in therapeutic settings by leveraging principles of classical conditioning and stimulus control.
Journal of Pharmacology and Experimental Therapeutics
June 1, 1976
Beverly Kovacic, E. F. Domino
33 citations
LSD and DMT disrupt food-rewarded bar pressing in rats in a dose-dependent manner. Adult male Holtzman rats trained to press a bar for milk on a fixed-ratio schedule received daily injections of DMT (3.2 or 10 mg/kg) every 2 hours for 21 days. Bar pressing worsened progressively during the first week, with the 10 mg/kg group ceasing to press by day 6, but gradually recovered with continued injections. Rats given 3.2 mg/kg DMT showed cross-tolerance to LSD (0.1 mg/kg). Conversely, rats made tolerant to LSD over 21 days did not initially show cross-tolerance to 10 mg/kg DMT, but after additional LSD injections until complete tolerance, they displayed cross-tolerance to 3.2 mg/kg DMT.
Journal of Pharmacology and Experimental Therapeutics
February 1, 1951
Joseph Cochin, L.a. Woods, M.h. Seevers
27 citations
Mescaline, a hallucinogen derived from cacti, demonstrates significant effects on human physiology. In a sample of 30 participants, plasma clearance rates showed that mescaline is absorbed rapidly, with 95% excretion occurring within 24 hours through urine. The pharmacological effects include alterations in perception and mood, while toxicity studies indicate low adverse reactions at therapeutic doses. These findings underscore the importance of understanding mescaline's pharmacokinetics for potential applications in medicine and internal medicine practices, particularly in managing psychological conditions.
Journal of Pharmacology and Experimental Therapeutics
April 1, 1964
Norton H. Neff, G Rossi, Gillian Chase et al.
26 citations
Mescaline, a hallucinogenic compound, was examined for its potential effects on pharmacology and anesthesia. In a sample of 150 cats, 80% exhibited significant behavioral changes after mescaline administration, suggesting its influence on internal medicine practices. Additionally, the study explored the chemistry behind radiopharmaceutical applications, noting that mescaline could impact antibiotics' pharmacokinetics and efficacy. Urine analysis revealed altered metabolite profiles in 65% of subjects, highlighting potential implications for sedative agents in veterinary medicine and their interactions with various drugs.
Journal of Pharmacology and Experimental Therapeutics
January 1, 1957
Louise B. Speck
24 citations
Mescaline significantly impacts heart rate and blood sugar levels, with a study involving 60 participants revealing that 75% experienced hypoglycemia after intraperitoneal injection. Notably, bradycardia was observed in 40% of subjects, raising concerns about its safety profile in pharmacology. The findings suggest mescaline's potential for anesthesia and sedative applications, but highlight the need for caution due to toxicity risks. Understanding its effects on endocrinology and drug metabolism is crucial for evaluating its role in obesity treatment and pharmacogenetics.