Serotonin hallucinations

Lysergic acid (LSD) Inhibitory effects of 5-hydroxytryptamine (5-HT) on neurons changes in intracellular serotonin Hallucinations... 

Methylenedioxymethamphetamine (MDMA ecstasy) is a synthetic analog of amphetamine that produces hallucinations, an elevation in mood, and a feeling of emotional closeness . This latter property has led to Ecstasy being referred to as the hug drag . The unique properties of Ecstasy as compared to the parent compound amphetamine are believed to be due to the more selective effects of Ecstasy in promoting transporter-mediated release of serotonin. The use of Ecstasy has become a part of the culture associated with rave style dance parties. 

Neuroleptics or antipsychotics suppress the positive symptoms of schizophrenia such as combativeness, hallucinations and formal thought disorder. Some also alleviate the negative symptoms such as affective blunting, withdrawal and seclusiveness. Neuroleptics also produce a state of apathy and emotional indifference. Most neuroleptics block dopamine D2-receptors but some, like clozapine, also block dopamine D4-receptors or serotonin 5-hydroxytryptamine2A-receptors. 

Schizophrenia is a chronic, complex psychiatric disorder affecting approximately 1% of the population worldwide. The chronic nature of the illness, in addition to the early age of onset, results in direct and indirect health care expenditures in the U.S., which amount to approximately 30 to 64 billion dollars per year [4]. It is perhaps the most devastating of psychiatric disorders, with approximately 10% of patients committing suicide. The dopamine hypothesis of schizophrenia postulates that overactivity at dopaminergic synapses in the central nervous system (CNS), particularly the mesolimbic system, causes the psychotic symptoms (hallucinations and delusions) of schizophrenia. Roth and Meltzer [5] have provided a review of the literature and have concluded a role for serotonin as well in the pathophysiology and treatment of schizophrenia. The basic premise of their work stems from the known interaction between the serotonergic and dopaminergic systems. 

MDMA stimulates the CNS, causes euphoria and relaxation, and produces a mild hallucinogenic effect. It can cause muscle tension, nausea, faintness, chills, sweating, panic, anxiety, depression, hallucinations, and paranoid thinking. It increases heart rate and blood pressure and destroys serotonin (5-HT)-producing neurons in animals. It is considered to be neurotoxic in humans. 

There is another reason why medications exert multiple effects. For example, an antidepressant that very specifically promotes serotonin neurotransmission and has little or no interaction with other receptor types will still produce multiple effects. How can this be Remember that in different areas of the brain, a single neurotransmitter can assume very distinct roles. When an individual takes a medication that alters the activity of a particular neurotransmitter, it generally does so throughout the brain. Consequently, the dopamine receptor blocking effect of haloperidol (Haldol) reduces hallucinations and paranoia in one brain region but causes upper extremity stiffness through its action in another brain region. 

LSD (lysergic acid diethylamide) Mimics serotonin, thus stimulating receptor Hallucination... 

Elko, C.J., Burgess, J.L., and Robertson, W.O. (1998) Zolpidem-associated hallucinations and serotonin reuptake inhibition a possible interaction. / Toxicol Clin Toxicol 36 195-203. 

In 1954, i.e. about 2 years after the discovery of chlorpromazine in Europe, two American biochemists (Woolley and Shaw) published the hypothesis that schizophrenia and similar psychoses could be based on a disturbance of serotoninergic neurotransmission in the brain. This hypothesis was supported by some facts that had become known shortly beforehand the spectacular psychotropic actions of LSD (lysergic acid diethylamide), which can trigger disturbances in perception, thought and feelings as well as hallucinations in healthy subjects (Stoll, 1947) and the serotonin-antagonistic effects of LSD, i.e. its ability to block the actions of serotonin in various pharmacological tests. 

A study conducted on 40 normals, this in Hungary some 30 years ago, found that the administration of 40 mg quantities to be symptom free. With several of the experimental subjects in this study, the DMT was preceded by the administration of 1-methyl-d-lysergic acid butanolamide (UML-491), a potent serotonin antagonist. This was given either orally (1-2 mg 30 to 40 minutes before) or intramuscularly (0.5 mg 10 minutes before). This served to greatly intensify the effects of the DMT, with intense and agitated hallucinations, highly intensified colors, and a more extreme loss of time and space perception. It was assumed that UML-491 was inactive, but recent trials indicate that there can be central effects produced. It is discussed in the entry for LSD. 

But how, exactly, does a toad secretion effect the human mind Bufotenin has a very close chemical similarity to serotonin, a substance used by the nervous system to transmit information from one nerve cell to another. Bufotenin overwhelms serotonin-sensitive cells and triggers effects ranging from hallucinations to seizures. Two Toronto men learned about this the hard way. They ended up in hospital after licking a cane toad they had purchased in a pet shop specializing in exotic animals. And a five-year-old Arizona boy did have a brush with death after he put a Colorado River toad into his mouth. (Just why he did this can only be explained by other five-year-old boys.) In any case, this species, bufo alvarias, is the most toxic toad in North America. The youngster developed seizures that had to be controlled with medication. 

Extension of this specificity principle to the clinical domain has resulted in the availability of increasingly well-aimed chemical bullets. If we wanted to block just one of the many serotonin receptors to see what would happen, we could probably do it But if we wanted to elevate mood in depression—or obsessive-compulsive disorder—would we expect the best result if we blocked just that one receptor And if we wanted to discourage auditory hallucinations in schizophrenia, would we want our drug to target only D2 dopamine receptors, even if we knew that the antipsychotic action of drugs correlated well with a drug s affinity for those receptors ... 

Of course, there is an important difference between LSD and dream hallucinations LSD images are often kaleidoscopic, whereas dream images are formed and scenario-like. And even though LSD causes an arrest of serotonin neuronal discharge, it does not enhance REM sleep. On the contrary, it promotes arousal both in humans and in animals, perhaps via the dopamine enhancement that links LSD to schizophrenia. 

Serotonin s effects include classical neuronal inhibition, as well as modulation. The study of dreaming teaches us that disinhibition is likely the cause of positive signs of hallucination, emotional intensification, and confabulation, whereas demodulation more likely causes the negative signs such as memory loss, disorientation, and bizarreness. Serotonin blockade induced disinhibition is one of the mechanisms by which the very same set of aspects of model psychoses is generated the visual distortion and hallucination could result from visual system disinhibition the emotional intensification could result from limbic system disinhibition and confabulation could result from associative cortex disinhibition. 

At higher doses, cocaine can produce undesirable effects, including tremor, emotional lability, restlessness, irritability, paranoia, panic, and repetitive stereotyped behavior. At even higher doses, it can induce intense anxiety, paranoia, and hallucinations, along with hypertension, tachycardia, ventricular irritability, hyperthermia, and respiratory depression. In overdose, cocaine can cause acute heart failure, stroke, and seizures. Acute intoxication with cocaine produces these various clinical effects, depending on the dose these effects are mediated by inhibition of the dopamine transporter and in turn by the effects of excessive dopamine activity in dopamine synapses, as well as by norepinephrine and serotonin in their respective synapses. 

Moreover, the absence of the release of serotonin in the brain has been correlated with the initiation of hallucinations. This is not to say that we can manipulate our diet to so undermine serotonin release as to experience a hallucination. We cannot. But certain drugs that will initiate this effect, and their action, as well as the experiences they produce, can tell us something about the normal function of serotonin in the brain. 

The complex sensory experience known as hallucinations can, however, occur from other sources besides drugs like LSD or psilocybin, and this fact may shed some light on the nature of the hallucinatory experience, drug-induced or otherwise, and its connection to serotonin. Consider, for example, the following hypothetical scenario ... 

Serotonin is not the only neurotransmitter whose manipulation can produce hallucinations. In fact, the neurotransmitter system introduced in Chapter 5 can be altered to cause similar hallucinatory effects and, for that matter, to bring about a host of experiences (e.g., euphoria) similar to those that occur with the manipulation of other neurotransmitters. 

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