User:Irvingca/Psychopharmacology

Evaluation
The lead section of the article is well written; however, it does not fully introduce some of the topics presented later in the article. According to the article's talk page, the most recent edit was in 2011; therefore, this article is likely not well up-to-date. The article does not seem to be missing much information; nonetheless, some of the information provided could be expounded upon further. This article does not employ many persuasive elements and focuses more on the factual information available about psychopharmacology than the presence of any controversy. Most of the issues I have noticed in the article are regarding the citations. There should be more citations and sources for this article and more citations that follow sentences about biochemical mechanisms of action for the different drug classes. The sources that are present in the article, however, are reliable sources and all of the links work. While the article is organized rather well, the writing may need some work. I have only noticed small grammatical errors, such as misplaced modifiers, diction and some syntax errors. The Talk page focuses on the correct portrayal of the attributes of some drugs and trying to differentiate the page from a psychiatric medicines page. The article is fairly well written and provides quality scientific information. There should be some more citations to account for the information that is listed, and the sentence structure of some parts could be tweaked. Overall, the article does feel incomplete.

My Possible Sources (With more to come)
Hart, C. L., & Ksir, C. (2022). Drugs, Society & Human Behavior. McGraw Hill Education.

Pollan, M. (2019). How to change your mind: The new science of psychedelics. Penguin.

Classical hallucinogens and neuroimaging: A systematic review of human studies: Hallucinogens and neuroimaging

Alcohol
Alcohol is a depressant, the effects of which may vary according to dosage amount, frequency, and chronicity. As a member of the sedative-hypnotic class, at the lowest doses, the individual feels relaxed and less anxious. In quiet settings, the user may feel drowsy, but in settings with increased sensory stimulation, individuals may feel uninhibited and more confident. High doses of alcohol rapidly consumed may produce amnesia for the events that occur during intoxication. Other effects include reduced coordination, which leads to slurred speech, impaired fine-motor skills, and delayed reaction time. The effects of alcohol on the body's neurochemistry are more difficult to examine than some other drugs. This is because the chemical nature of the substance makes it easy to penetrate into the brain, and it also influences the phospholipid bilayer of neurons. This allows alcohol to have a widespread impact on many normal cell functions and modifies the actions of several neurotransmitter systems. Alcohol inhibits glutamate (a major excitatory neurotransmitter in the nervous system) neurotransmission by reducing the effectiveness at the NMDA receptor, which is related to memory loss associated with intoxication. It also modulates the function of GABA, a major inhibitory amino acid neurotransmitter. Abuse of alcohol has also been correlated with thiamine deficiencies within the brain, leading to lasting neurological conditions that affect primarily the ability of the brain to effectively store memories. One such neurological condition is called Korsakoff's Syndrome, for which very few effective treatment modalities have been found. The reinforcing qualities of alcohol leading to repeated use – and thus also the mechanisms of withdrawal from chronic alcohol use – are partially due to the substance's action on the dopamine system. This is also due to alcohol's effect on the opioid systems, or endorphins, that have opiate-like effects, such as modulating pain, mood, feeding, reinforcement, and response to stress.

Antidepressants
Antidepressants reduce symptoms of mood disorders primarily through the regulation of norepinephrine and serotonin (particularly the 5-HT receptors). After chronic use, neurons adapt to the change in biochemistry, resulting in a change in pre- and postsynaptic receptor density and second messenger function. The use of antidepressants originates from the Monoamine Theory of Depression and Anxiety, which states that the disruption of the activity of nitrogen containing neurotransmitters (i.e. serotonin, norepinephrine, and dopamine) is strongly correlated with the presence of depressive symptoms.

Monoamine oxidase inhibitors (MAOIs) are the oldest class of antidepressants. They inhibit monoamine oxidase, the enzyme that metabolizes the monoamine neurotransmitters in the presynaptic terminals that are not contained in protective synaptic vesicles. The inhibition of the enzyme increases the amount of neurotransmitter available for release. It increases norepinephrine, dopamine, and 5-HT and thus increases the action of the transmitters at their receptors. MAOIs have been somewhat disfavored because of their reputation for more serious side effects.

Tricyclic antidepressants (TCAs) work through binding to the presynaptic transporter proteins and blocking the reuptake of norepinephrine or 5-HT into the presynaptic terminal, prolonging the duration of transmitter action at the synapse.

Selective serotonin reuptake inhibitors (SSRIs) selectively block the reuptake of serotonin (5-HT) through their inhibiting effects on the sodium/potassium ATP-dependent serotonin transporter in presynaptic neurons. This increases the availability of 5-HT in the synaptic cleft. The main parameters to consider in choosing an antidepressant are side effects and safety. Most SSRIs are available generically and are relatively inexpensive. Older antidepressants, such as the TCAs and MAOIs usually require more visits and monitoring, and this may offset the low expense of the drugs. The SSRIs are relatively safe in overdose and better tolerated than the TCAs and MAOIs for most patients.

Psychedelic Hallucinogens
Hallucinogens cause perceptual and cognitive distortions without delirium. The state of intoxication is often called a “trip”. Onset is the first stage after an individual ingests (LSD, psilocybin, or mescaline) or smokes (dimethyltryptamine) the substance. This stage may consist of visual effects, with an intensification of colors and the appearance of geometric patterns that can be seen with one's eyes closed. This is followed by a plateau phase, where the subjective sense of time begins to slow and the visual effects increase in intensity. The user may experience synesthesia, a crossing-over of sensations (for example, one may “see” sounds and “hear” colors). These outward sensory effects have been referred to as the "mystical experience;" and current research suggests that this state could be beneficial to the treatment of some mental illnesses, such as depression and possibly addiction. In instances where some patients have seen a lack of improvement from the use of antidepressants, serotonergic hallucinogens have been observed to be rather effective in treatment.  In addition to the sensory-perceptual effects, hallucinogenic substances may induce feelings of depersonalization, emotional shifts to a euphoric or anxious/fearful state, and a disruption of logical thought. Hallucinogens are classified chemically as either indolamines (specifically tryptamines), sharing a common structure with serotonin, or as phenethylamines, which share a common structure with norepinephrine. Both classes of these drugs are agonists at the 5-HT2 receptors; this is thought to be the central component of their hallucinogenic properties. Activation of 5-HT2A may be particularly important for hallucinogenic activity. However, repeated exposure to hallucinogens leads to rapid tolerance, likely through down-regulation of these receptors in specific target cells. Research suggests that hallucinogens affect many of these receptor sites around the brain and that through these interactions, hallucinogenic substances may be capable of inducing positive introspective experiences. The current research implies that many of the effects that can be observed occur in the occipital lobe and the frontomedial cortex; however, they also present many secondary global effects in the brain that have not yet been connected to the substance's biochemical mechanism of action.

Dissociative Hallucinogens
'''Another class of hallucinogens, known as dissociative hallucinogens, includes drugs such as Ketamine, Phencyclidine (PCP), and Salvia Divinorum. Drugs such as these are thought to interact predominantly with glutamate recpetors within the brain. Specifically, ketamine is thought to block NMDA receptors that are responsible for signalling in the glutamate pathways. Ketamine's more tranquilizing effects can be seen in the central nervous system through interactions with parts of the thalamus by inhibition of certain functions. Ketamine has become a major drug of research for the treatment of depression. These antidepressant effects are thought to be related to the drug's action on the glutamate receptor system and the relative spike in glutamate levels, as well as its interaction with mTOR, which is an enzymatic protein involved in catabolic processes in the human body. Phencyclidine's biochemical properties are still mostly unknown; however its use has been associated with dissociation, hallucinations, and in some cases seizures and death. Salvia Divinorum, a plant native to Mexico, has strong dissociative and hallucinogenic properties when the dry leaves are smoked or chewed. The qualitative value of these effects, whether negative or positive, has been observed to vary between individuals with many other factors to consider.'''

(Add information about ketamine trials, salvia research and ibogaine studies). ''Instructor feedback: A couple of recommendations on your sandbox edits. First, I would bring over more of the article and the general outline for the article so reviewers (me and your peers) can get a better idea of the flow. Second, I would change the term "positively" to positive. So far, nice work on these edits and I am excited to see what additions you plan for your article!''