Analytical Essay on LSD: History, Effects, and Mechanisms

LSD, also known as Lysergic acid diethylamide-25 is a potent drug that is in fact, the most powerful out of all of the hallucinogens psychedelic drugs, this is due to the fact that is is approximately 100 times stronger than psilocybin and 4000 times stronger than mescaline. This drug changes a person’s mental state by changing, altering, and distorting the perception of reality to the point where at high doses hallucination occurs. LSD is synthetically made from lysergic acid, which is found in ergot, a fungus that grows on rye and other grains. The effects of LSD are so potent that its doses tend to be in the microgram range. This paper seeks to evaluate the effects, history and chemical mechanisms of LSD. In addition, this article attempts to uncover and bring to light some of the effects that LSD has on various brain structures and explain how those effects come into fruition, as well as the potential of it being a treatment. Ultimately, the paper suggests that more research is needed into LSD being a potential treatment and that the stigma against LSD needs to end.

Nearly half a century ago, psychedelics “fell from medical grace” and little to no research has been conducted about these substances, which is potentially detrimental if it does pose qualities that it can be a good medication. However, some new research and studies pose some suggestions that some researchers have faith that LSD can be studied more in depth in the future. (Langlitz, 2013). Hallucinogens do not always instigate hallucinations, despite it’s somewhat misnomer of a name. The user is under the false sensations, in which the experience is limited to themselves. Hallucinogens prompt and induce the user to act and say things that they would normally not do. In short, they shift and change the usual or typical personality of the individual. LSD has generally always been viewed as highly controversial in the North Americas and worldwide/internationally, however, this usually is due to the tragic fact that because people have been exposed to media bias or miseducated about its effects. Its physiological effects on the brain and body have continued to become increasingly well-known during the past few decades, a time when research in neuroscience was at its height and peak. The psychological effects of LSD have often been difficult to describe and document very well as they were first accidentally discovered on the fateful day of April 16, 1943 by the research chemist Albert Hofmann. This was due to a small amount of the drug soaking/leaking into his fingers during the interim of a routine scientific synthesis. Hofmann had described an experience in which he was situated in an imaginative, fantasy dream-like state for a 2-3 hour long timeframe. The drug is usually classified as an indocile hallucinogen. It is additionally, encompassed within the confines of the phantastica family. To make sense of this, what this means is that it contains the structure which is known and referred to as the indole nucleus, which is in conjunction with the simplest structure of serotonin, a neurotransmitter. This drug is entirely capable of altering and changing one’s perceptions while enabling the individual to remain in communication within the current world, this means that somebody who is high from LSD or under the influence of this drug will often be simultaneously conscious of both the 'real' world and the 'fantasy' world, which is the namesake of the category Phantastica (Ray & Ksir, 1996).

History of LSD

LSD has the presentation of being a white-coloured, odorless crystalline powder that has the unique characteristic of being water-soluble. It also has the feature of breaking down under the exposure to the ultraviolet (UV) light. Lysergic Acid Diethylamide, better known as LSD and was first synthesized by Albert Hofmann on November 16, 1938. The discovery took place in Basel, Switzerland, in Author Stroll’s Sandoz Laboratories. In 1943, the effects were discovered in 1943 by the Swiss chemist Albert Hofmann, who was working there and had accidentally dosed himself and was astonished by the psychoactive effects of a drug he had labeled LSD-25. Hofmann had been working with ergot, a rye fungus in the hope of creating a new and improved, as well as more advanced cardiovascular stimulant.

Worldwide, in clinical research settings revived investigations are taking place that are learning about and testing the use and consumption of psychedelic substances for treating illnesses such as addiction, depression, anxiety and posttraumatic stress disorder (PTSD). Since the termination of a period of research from the 1950s to the early 1970s, most psychedelic substances have been classified as drugs that have a high likelihood or chance of being abused with little to no recognized medical value. However, recent controlled clinical studies have been conducted to appraise the basic psychopharmacological properties and therapeutic adequacy of these drugs as additional appendages to already existing psychotherapeutic approaches. What is most integral to this revival is the re-emergence of an archetype that understands and acknowledges the crucial importance of set (i.e., psychological expectations), setting (i.e., physical environment) and the therapeutic clinician–patient relationship as the most essential elements for facilitating positive healing experiences and accomplishing positive and happy outcomes.1,2 The public is often well notified in the potential harmful effects and pitfalls of psychedelic drugs, but much of this knowledge stems from cases involving patients who used illicit substances in unsupervised nonmedical contexts without considering the usage of LSD in a more controlled environment. Emerging research for therapeutic purposes associated with human subjects needs to be discussed and addressed in a great amount of detail, in lieu of both the possible benefits and the potential risks and harms of using psychedelic agents as sidedicks to psychotherapy or counselling for profound psychological effects.

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Effects of LSD

An ostensibly insignificant minute dose of LSD can dramatically adjust one’s perception of reality to the extent where of hallucination occurs. What this means is that the consumer’s perception of reality is changed by seeing things that do not exist and are not present in this reality. LSD is an intensely powerful substance which can dramatically alter the mood, perception, as well as a variety of cognitive processes of the human mind. It can also dramatically reshape the imagination as well as cause an effect, known as synesthesia. When the person takes LSD, they will feel that the very nature of reality itself is amplified and enhanced through this use. There are quite a large variety of effects for the use of LSD, both physically and mentally, as well as short and long term. Some physical effects include but are not limited to dilated pupils, higher or lower body temperature, sweating and/or chills, loss of appetite, insomnia, lack of saliva in the mouth, and tremors. Some mental effects include delusions, visual hallucinations, an artificial sense of euphoria, the distortion of one’s sense of time and identity, impaired depth and time perception as well as the distorted or false perception of the shape and size of movements, touch, objects, sounds, colour, and the user’s own body image, severe, terrifying thoughts and feelings, the fear of losing control, panic attacks, flashbacks, and severe long-term depression or psychosis. The long-term effects of LSD use can be both good and bad. There are cases of people who claim to have had their entire lives turned around, for the better, due to LSD use. On the other hand, some people have been hospitalized due to the effects of LSD psychosis. However, even though there are all of these effects, psychedelics are considered and contemplated to be safe physiologically and are said not to produce either the results of dependence or addiction. There are no recorded overdose deaths due to the ingestion of LSD at what are considered to be reasonable dosages. The user's mood is very likely to adjust depending on how he/she feels emotionally at various stages during the usage of LSD. The quality of the outcome of the use of LSD is almost always dependent on two extremely important factors: the set and the setting. The set refers to a user's expectations of how it feels to take the drug and how the mind changes. The setting is the environment in which the drug is taken. For example, an inexperienced user takes LSD while they are in a stressed condition or in a bad mood, a bad experience may most likely occur. By the same token, taking LSD in a chaotic environment like a noisy concert could turn into trouble for someone unsure of the drugs effects. When users on LSD become frightened or enter a state of panic, they can usually be relieved or calmed down by nearby.

Mechanisms of LSD

LSD affects the brain by stimulating the serotonin 5-HT2A brain receptor subtype. Psychedelics such as LSD are either agonists or partial agonists. This particular receptor is a member of the Family A type G protein-coupled receptors (GPCRs) and is widely expressed throughout the brain, being particularly dense on apical dendrites of layer 5 cortical pyramidal cells. Its canonical signaling occurs through coupling to Gaq, activating phospholipase C, resulting in phosphoinositide hydrolysis, formation of diacylglycerol, and leading to mobilization of intracellular calcium. Activation of the 5-HT2A receptors on the glutamatergic neurons within the brain leads to the cells to become more excitable. It generally does not, however, lead to the depolarization and the generation of action potentials. There is significant expression of the receptors in the 5th layer in the medial prefrontal cortex, reticular nucleus of the thalamus, ventral tegmental area, the amygdala, the locus coeruleus, as well as a few other key regions. However, the claustrum is the part of the brain which depicts the highest expression of 5-HT2A receptors in the brain. Psychedelics cause a brain effect that leads to cortical cell excitation through suppressing raphe cell firing in the brain stem through 2 methods: either directly (LSD and similar compounds) or indirectly (by phenethylamines). These generally lead to cortical cell excitation. The activation of 5-HT2A receptors in so many key brain regions lead to neuronal excitability and therefore would be expected to have marked effects on cognition. Regarding substance abuse, it has been proven and demonstrated that by multiple surveys, researchers, and analysts that anxiety and stress are very important triggers for a relapse. It is possible that the 5HT2A receptor downregulation by hallucinogens may help in stress-induced relapses. LSD may also trigger effects to the brain such as brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF). Both of these effects play important roles in neurogenesis, synaptic plasticity, learning, and memory. There is evidence that LSD may induce neuroplastic changes suggesting a basis for the persistent behavioral changes.

How can LSD be used clinically?

The pharmacology of LSD is inadvertently complex, even in today’s entrenched, incessant research, its mechanisms of action remain unclear to this day. LSD is physiologically well tolerated and there is no evidence of its virulency for long-lasting debacles to the brain and other comer parts of the human organism. The review of pharmacology, psychopharmacology, related preclinical research, as well as basic studies with human subjects are gleaned from the incessant research that was for the most part conducted in the 1950s and 1960s during an era that held great promise and fostering for LSD and related hallucinogens. Expentation, confidence, and sanguineness was placed in these unique substances for new and contemporary treatments for psychiatric conditions and discoveries that would enhance our circumscribed knowledge of the mind. The confidence placed on LSD and other hallucinogens showed promising results, as hallucinogen research did indeed lead to the discovery of serotonin, brain second-messenger systems, and a variety of other research techniques such as prepulse inhibition and the use of animals for detection of activation of specific sub-receptors. The once-innovative research of LSD diminished and was slowly phased out after these prodigious advancements. The clinical promises failed to be addressed by analysts and the public while illicit use of hallucinogens pressured governments into taking strict police action against such use of the new-found drug. Government funding of research dried up, as well, and a generation of scientists moved on to other more seemingly important topics. Today, LSD and other hallucinogens are once again being appraised and evaluated on, for specific purposes, such as for treatment of the “cluster headache” and as tools in therapy for working with those suffering from anxiety provoking end-of-life issues and for posttraumatic stress disorder (PTSD). As these new studies further advance in knowledge, and move forward, it is anticipated by today’s researchers and many people part of the medical industry the current research taking place will be a roadmap for also securing the data missing from our knowledge of the pharmacology of LSD from our past research. In the past LSD and other hallucinogens have been used in professional studies of the human mind. These studies have had mixed results, that always almost always vary, depending on the patient and his or her surroundings during consumption and testing. Emerging research is beginning to change the public and the industries perception of LSD from a drug that can negatively affect the mental and physical well-being, to one that can alleviate the visual and hidden symptoms of anxiety and depression. Its benefits are also being thoroughly studied in relation to helping struggling individuals who are trying to overcome drug dependency. The most remarkable and unique potential benefit of hallucinogens is what's known as 'ego death,' an experience in which people lose their sense of self-identity and, as a result, are able to detach themselves from worldly concerns like a fear of death, addiction, and anxiety over temporary — perhaps thoroughly exaggerated — traumatic or amazing life events. When people take a potent dose of the psychedelic, they can experience watershed spiritual, hallucinogenic trips that can make the user feel like they're transcending their own bodies and even time and space. This, in turn, gives people a lot of perspective — as if they can see themselves as a small part of a much broader, seemingly magical universe, it's a lot easier, and often unhesitant of them to discard personal, relatively insignificant and inconsequential concerns about their own lives and death. Today, the studies of LSD have resumed and are being used regularly to clinical patients.

Conclusion

The recent rejuvenation of scientific interest in psychedelic medicine is generating new knowledge about a class of unique pharmacologic substances that patients and medical professionals have long used and needed. As this field of research continues to evolve with resumed research, the current educational system for many medical schools may need to be updated to include the latest knowledge, breakthroughs, and research about psychedelic drugs. This would include new scientific evidence about the relative risks and harms of psychedelic drugs - which is profoundly absent in current drug control scheduling classifications and advertisements, they should also consider the adverse outcomes from uncontrolled recreational use rather than supervised clinical settings (Nichols, David). So considering new laws and regulations revolving around the use of pharmacologic substances is important. In addition to all of that, it would encompass knowledge about the potential therapeutic uses of these agents, particularly because patients may query their physicians about research findings reported in the media. If further scientific evidence accumulates on the therapeutic value of psychedelic medicines, specialized, professional clinical training for physicians, nurses, psychologists and other health professionals will need to be required to meet a future with an increased demand for such treatments. It is important for policy-makers to be aware of and open to new approaches to treatments emerging in the field of psychedelic medicine. This is thoroughly important for those who are concerned about the vastly growing prevalence of mental illness, including addiction, as well as its associated human, social and economic costs. Currently, international drug control scheduling classifications and popular misconceptions about the relative risks and harms of psychedelic drugs make research involving humans difficult. However, continued medical research and scientific inquiry into psychedelic drugs may offer new ways to treat mental illness and addiction in patients who do not benefit from currently available treatments.

The re-emergence of the studies of psychedelic medicine has the potential to allow gaping access to therapeutic and clinical doors that were closed for far, far too long. The dangers of LSD are considered miniscule when compared to other drugs, despite the fact of it being one of the most potent out of all hallucinogenic drugs. It doesn’t promote either addiction or dependence, which are damning feature of most drugs. There is new evidence that supports the idea of a new age of psychedelic medicine may be upcoming and plausible in the future, as suggested by the legalisation of marijuana as well as the use of medical marijuana.