Effects Of Mescaline Research Articles

Novel, Unifying Mechanism for Mescaline in The Central Nervous System: Electrochemistry, Catechol Redox Metabolite, Receptor, Cell Signaling and Structure Activity Relationships

A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines, and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting. There is a discussion of receptor binding, electrical effects, cell signaling and other modes of action. Mescaline is a nonselective, seretonin receptor agonist. 5-HTP receptors are involved in the stimulus properties. Research addresses the aspect of stereochemical requirements. Receptor binding may involve the proposed quinone metabolite and/or the amino sidechain via protonation. Electroencephalographic studies were performed on the effects of mescaline on men. Spikes are elicited by stimulation of a cortical area. The potentials likely originate in nonsynaptic dendritic membranes. Receptor-mediated signaling pathways were examined which affect mescaline behavior. The hallucinogen belongs to the class of 2AR agonists which regulate pathways in cortical neurons. The research identifies neural and signaling mechanisms responsible for the biological effects. Recently, another hallucinogen, psilocybin, has been included within the unifying mechanistic framework. This mushroom constituent is hydrolyzed to the phenol psilocin, also active, which is subsequently oxidized to an ET o-quinone or iminoquinone.

Effects of mescaline and some of its analogs on cholinergic neuromuscular transmission

Mescaline (3,4,5-trimethoxyphenylethylamine; MES) and its analogs, anhalinine (ANH) and methylenemescaline trimer (MMT) were investigated, using sciatic-sartorius preparations of the frog and cortical tissue from the rat. The effects of MES and its analogs were examined with respect to muscle twitch, resting membrane potential and nicotinic receptor binding. Mescaline and its analogs (10–100 μM) blocked both directly and neurally evoked twitches but their effects on neurally evoked twitches were greater than those on directly evoked twitches. Mescaline, ANH and MMT decreased amplitude of the maniature endplate and endplate potentials, decreased acetylcholine (ACh) quantal content, hyperpolarized the resting membrane potential and prolonged duration of the action potential. They did not significantly displace the binding of [ 125I]-α-bungarotoxin (α-BTX)vto nicotinic receptors, at concentrations which blocked neuromuscular transmission. These results suggest that MES and its analogs inhibit cholinergic neuromuscular transmission by blocking release of ACh; they also affect K + conductance.

Klüver, Bucy, and the Klüver-Bucy Syndome

ABSTRACT.While exploring the effects of mescaline in primates, Kluver and Bucy fortuitously discovered that placidity occurred after temporal lobectomy in the ferocious female rhesus monkey, “Aurora.” Elaboration on this in a series of three articles published between 1937 and 1939 eventually led to what is recognized today as the Kluver-Bucy syndrome (KBS). This syndrome is highlighted by inability to recognize objects visually (visual agnosia), hypermetamorphosia or loss of habituation to repetitive stimuli, eating disorders (bulimia), loss of normal fear and anger responses, and altered sexual behavior. Its equivalent in humans is further complicated with dementia, amnesia, and aphasia, and it has been encountered in association with many clinical conditions ranging from porphyria to adrenoleukodystrophy. KBS is currently understood as a disorder of cross-modal association due to interruption of the bidirectional amygdalocortical network mediated by opiate-containing fibers. KBS is of interest to epile...

Effects of intraocular mescaline and LSD on visual-evoked responses in the rat.

The effects of mescaline and LSD on the flash-evoked cortical potential (FEP) were determined in unrestrained rats with chronically-implanted electrodes. Systemic administration of mescaline or LSD significantly attenuated the primary component of the FEP at three stimulus intensities with the greatest effect observed 60-90 minutes following drug administration. The magnitude and specificity of the effects of these agents on the primary response suggest that they produce deficits in conduction through the retino-geniculato-cortical system. The serotonin receptor antagonists, cyproheptadine and methysergide, antagonized the mescaline-induced depression of the FEP in accordance with neurochemical and behavioral evidence that mescaline acts as a partial agonist on serotonin receptors. Topical or intraocular administration of atropine antagonized the actions of systemically-administered mescaline. In addition, intraocular administration of mescaline or LSD attenuated the FEP indicative of an action of these hallucinogens on visual processing in the retina which is modulated by muscarinic receptor activity.

6-Hydroxydopamine inhibits some effects of mescaline centrally administered to rabbits

The narcotic antagonist naloxone does not antagonize antinociception elicited in the rabbit by 100 microgram/kg of mescaline centrally administered, whereas pretreatment with 6-hydroxydopamine (6-OHDA) inhibits this mescaline effect. Stereotyped behavior of rabbits following central mescaline administration is also prevented by 6-hda pretreatment. Since 6-OHDA in known to produce a degeneration of catecholamine containing nerve terminals, a crucial role of catecholamines is suggested in the complex of effects seen in the rabbit after central administration of the hallucinogen.

Development of tolerance to the antinociceptive effect of mescaline intraventricularly administered to rabbits.

Some effects of intraventricular injection of mescaline are examined in conscious rabbits. By means of electrical stimulation of the tooth pulp it is shown that an acute treatment with 70, 100, 150 mug/kg of mescaline elicits analgesia, the intensity of which is dose-dependent: with daily administration of 100 mug/kg for 5 days a complete tolerance develops to the antinociceptive effect. A tolerance also develops to the behavioral effects of mescaline after repeated administrations, with the exception of the stuporous state, a symptom which, on the contrary, is accentuated as the treatment proceeds. An EEG arousal is induced in the rabbit by acutely administered mescaline; the chronic treatment (100 mug/kg) makes the return of voltage to original levels progressively slower. Finally, the confrontation of certain of the mescaline-induced effects with those of morphine suggests some biochemical and neural patterns common to the 2 drugs.

Parachlorophenylalanine potentiates facilitatory effects of mescaline on shuttlebox escape/avoidance in rats.

Acute parachlorophenylalanine (pCPA) pretreatment (150 mg/kg, i.p., 24 h beforehand) potentiated facilitatory effects of mescaline (39.6 mg/kg i.p.) on shuttlebox escape/avoidance in hooded rats, tested in two different situations: 1. during aquisition of avoidance behavior (Experiment 1); and 2. in stable pretrained poor avoiders (Experiment 2). pCPA alone did not influence avoidance behavior in either situation. Mescaline, with pCPA pretreatment, may be associated with long-term behavioral effects; all rats treated with this combination were later found to be poor avoiders, unable to achieve a stable baseline of good avoidance. pCPA significantly depleted brain norepinephrine and dopamine, as well as serotonin, measured after testing in the second situation.

The effects of 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-ethylamphetamine (DOET), d-amphetamine, and cocaine in rats trained with mescaline as a discriminative stimulus.

The effects of mescaline (3,4,5-trimethoxyphenylethylamine), a hallucinogen, can function as a discriminative stimulus in appropriately trained rats. As a test of the hypothesis that those pharmacologic properties which distinguish hallucinogens and non-hallucinogens in man are reflected in distinctive stimuli in rats, the present experiments examined the effects of 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-ethylamphetamine (DOET), d-amphetamine, and cocaine in rats trained with mescaline as a discriminative stimulus. Administration of a range of doses of DOM and DOET to subjects in which saline functioned as SD and mescaline as Sdelta revealed that a dose of 0.3 mg of either DOM or DOET was equivalent to the training dose of mescaline. When tested in rats in which mescaline served as SD, DOM and DOET were likewise found to mimic mescaline. In contrast, doses of d-amphetamine and cocaine (1 and 30 mg/kg, respectively) which were equivalent to the training dose of mescaline as Sdelta, did not result in responding appropriate for the mescaline condition when mescaline was trained as SD. When DOET (0.3 mg/kg) was substituted for saline as Sdelta, no evidence of discriminated responding was obtained in the course of 50 sessions. The present data, in conjunction with previous observations, suggest that those effects of mescaline in the rat which function as a discriminative stimulus are better correlated with pre-hallucinogenic LSD-like activity in man then with hallucinogenic activity per se. Thus, these effects in rats represent a necessary but not a sufficient condition for prediction of hallucinogenic activity in man.

Effects of mescaline, [ Δ9]-tetrahydrocannabinol and pentobarbital on the auditory evoked responses in the cat

Effects of mescaline, [ Δ 9]-tetrahydrocannabinol ([ Δ 9]-THC) and pentobarbital were studied on the peak latency, area and amplitude of the waves (positive P 1 and negative N 1) of the averaged auditory evoked potentials in restrained conscious cats. Mescaline (5–15 mg/kg i.p.) caused a significant increase in peak latency (8–13%), area (77–195%) and amplitude (38–128%) of these waves. The onset of these changes was within 10–40 min and their duration ranged between 90–180 min. [ Δ 9]-THC (0.5–2 mg/kg in 4% Tween 80 i.p.) also caused a marked increase in peak latency, area and amplitude (10–25%, 113–370% and 66–310% respectively), while Tween 80 caused slight and variable effects. The effects of [ Δ 9]-THC had its onset within 40–105 min and lasted for more than 120–180 min. Pentobarbital (20 mg/kg i.p.) also caused an increase in the peak latency (8–23%), area (94–121%) and amplitude (119–132%) of these waves within 5–7 min. The peak effect occurred within 10–15 min and lasted for more than 100–120 min. These effects of the hallucinogens, mescaline and [ Δ 9]-THC thus appear to resemble those of pentobarbital, a central nervous system depressant; however the mechanism of their actions differs.

Some neurochemical and neuropharmacological studies on the interactions between mescaline and 1-methyl-1,2,5,6-tetrahydropyridine-3-(N,N-diethylcarboxamide) (THPC).

The effect of THPC was studied on some pharmacological and neurochemical changes induced in the rat by mescaline. The results show that THPC antagonizes the effect of mescaline on the calorigenic action of a methyl-m-tyrosine in reserpinized mice. THPC potentiated the depletion of brain dopamine caused by H77/77 in combination with mescaline. In none of the other pharmacological or neurochemical tests was there any evidence that THPC antagonized or potentiated the effects of mescaline.

Effect of mescaline on single cortical neurones.

The effects of mescaline upon single cortical neurones were studied, using the microiontophoretic technique. Mescaline elicited excitatory and depressant responses similar to those evoked by noradrenaline (NA) and 5-hydroxytryptamine (5-HI). The responses to NA and mescaline were usually in the same direction, the neurone being either excited by both drugs or depressed by both drugs. The correlation between the effects of mescaline and 5-HT, however, was less consistent. The beta-adrenoceptor blocking agent MJ-1999 and the 5-HT antagonist methysergide were both effective in antagonizing mescaline responses.

Effects of mescaline and 2,5-dimethoxy-4-methylphenethylamine on sleeping time in mice.

Effects of mescaline and 2,5-dimethoxy-4-methylphenethylamine on sleeping time in mice.

The effects of mescaline, amphetamine and four-ring substituted amphetamine derivatives on spontaneous brain electrical activity in the cat

Alterations in frequency distribution of spontaneous brain electrical activity were measured following administration of mescaline, amphetamine, trimethoxy-amphetamine (TMA), methoxy-methylenedioxy-amphetamine (MMDA), methylenedioxy-amphetamine (MDA) and dimethoxy-amphetamine (DMA) to unanesthetized and unrestrained cats. Two orthogonal patterns of frequency change were found which were correlated with dosage of the test compounds. It is proposed that one of these patterns represents central alerting in the cat, while the other is a correlate of the hallucinogenic effect produced in man by some of the drugs used. An analysis of the effects produced by individual compounds for their content of each pattern revealed that only amphetamine produced significant alerting; in terms of hallucinogenic effect, activities of the drugs decreased in the order TMA > MDA > MMDA > mescaline > DMA.

Cross tolerance between mescaline and LSD-25, with a comparison of the mescaline and LSD reactions.

1. The reactions caused by intramuscular administration of 0.75 mcg/ kg and 1.5 meg/kg of LSD-25 have been compared in the same 10 subjects with those induced by 2.5 mg/kg and 5.0 mg/kg of mescaline. 2. Both LSD and mescaline caused dilatation of the pupils, increase in body temperature, elevation of pulse rate and increase in systolic blood pressure. Both drugs decreased the threshold for elicitation of the kneejerk. 3. After both drugs, similar abnormal mental states characterized by anxiety, difficulty in thinking, alteration in mood (generally euphoric), altered sensory perception (particularly visual), elementary and true visual hallucinations and alterations of body image were reported by the subjects. 4. The effects of mescaline appeared more slowly and persisted somewhat longer than did the effects of LSD. 5. LSD tartrate is 2400–4900 times as potent as mescaline hydrochloride. On a molecular basis, LSD is 4500 to 9275 times as potent as mescaline. 6. Patients receiving LSD daily developed direct tolerance to LSD; such patients were also cross tolerant to mescaline. Likewise patients receiving mescaline daily became tolerant to mescaline and cross tolerant to LSD. 7. It was inferred that LSD, psilocybin and mescaline probably share common mechanisms of action or some common final pathway.

Drugs in emotional disorders: past and present.

Excerpt Widespread interest in drugs currently used for treating emotional disorders has created the erroneous impression that pharmacologic approaches to psychiatric treatment are something new. B...

A stereotyped response induced by mescaline in mice as a means of investigating the properties of drugs acting on the CNS.

Abstract The effects of mescaline on spontaneous activity of mice placed in special cages have been studied. The typical response (stereotyped response) has been recorded and assessed in terms of percentage of animals showing the effect. Among drugs affecting the response chloropromazine shows the highest specificity. Promazine, hexobarbitone and pentobarbitone also show a definite but minor effect in doses that do not impair motor function. The response is little affected by phenobarbitone. Meprobamate, mephenesin and a thiadiazole derivative (L 1458) at non-paralyzing doses, and also azacyclonol, do not produce specific antagonistic effects. Nor is the effect significantly influenced by atropine, but it is enhanced by morphine.

Effects of mescaline in laboratory animals and influence of ataraxics on mescaline-response.

SummaryMescaline, injected intravenously and intraperitoneally into dogs and cats and into the lateral ventricle of the brain of cats, produced acute autonomic effects followed by catatonia. These responses appeared to be altered or prevented by pretreatment with the ataraxic agents chlorpromazine, reserpine, and azacyclonol.We are indebted to Dr. Robert L. Craig and Mr. Robert G. Bianchi for implanting the cranial cannulae and to Dr. Kurt Rorig for synthesizing the azacyclonol.

Effects of mescaline, LSD-25, and adrenochrome on depth electrograms in man.

In a recent report concerning the reversibility by chlorpromazine of psychoses induced by means of mescaline andd-lysergic acid diethylamide (LSD-25), careful attention was given to the clinical and electroencephalographic changes.1Although the clinical changes of this reversal effect were immediate and striking, the conventional electroencephalographic changes were minimal, and it was difficult to assess them. It was noted in another recent study that mescaline and LSD-25 failed to activate temporal-lobe epilepsy either clinically or electroencephalographically.2 Because of these factors, it was hoped that depth electrographic studies might be fruitful in elucidating the effects of these drugs. It was hoped also that study by means of depth electrography of the effects of adrenochrome might elucidate its reported actions of inducing a psychosis without insight in volunteers3and increasing the paroxysmal discharges in the electroencephalograms of epileptics.4Scalp electroencephalography and depth electrography were undertaken as specific

Certain Effects of Mescaline and Lysergic Acid on Psychological Functions

(1954). Certain Effects of Mescaline and Lysergic Acid on Psychological Functions. The Journal of Psychology: Vol. 38, No. 1, pp. 211-221.

Effects of mescaline and lysergic acid (d-LSD-25).

The effects of mescaline and lysergic acid were studied in schizophrenic patients. It was found that physiological changes were produced in these patients and that their mental symptomatology was markedly aggravated. The observations made with the above-mentioned drugs on normal individuals were compared with those seen in schizophrenic patients. Mescaline and lysergic acid are drugs that disorganize the psychic integration of a person. This disorganization is much more apparent in schizophrenics than in normals. The diagnostic, prognostic, and therapeutic use of these drugs is also discussed.