LSD: Principles and Negative Consequences

Introduction

Lysergic acid diethylamide (LSD) also colloquially known as “acid” is a psychedelic drug often criticised as being dangerous and delusion inducing but is also heralded by many scientists and psychologists as mind expanding, wonder drug. LSD is a derivative of ergot; ergot is a fungus which frequently grows on both rye and wheat. For centuries ergot was utilised as a medicine, such as in childbirth in small dosages. It was used to aid childbirth via both quickening delivery and stopping the bleeding afterwards. So intuitively a pharmaceutical company began to research its potential medical benefits. Sandoz Laboratories tasked chemist Albert Hoffman in the early 20th century with identifying and isolating the compounds in ergot that were medically beneficial. In 1938 he tried a few variations which yielded little success. Although on a few animal experiments Hoffman noted that one variation, Lysergic acid diethylamide -25 or LSD-25 had a peculiar effect on the mice, resulting in the species bizarrely behaving in an excited manner. Despite this Sandoz thought very little of the compound and mostly forgot about it. For Hofmann however, this wasn’t the case, as 5 years later in 1943 he resynthesised the compound and one day, while working with it began to feel strange. Hoffman went home laid down and became the first person in the world to hallucinate on LSD. But he couldn’t determine what caused the hallucination, as he always took extra precautions avoiding ingestion knowing that LSD could be poisonous. This led Hoffman to conclude that he absorbed a minute amount through his fingertips. He then began to experiment on himself by dosing himself with 250µg. The rest is history, LSD became a centrepiece of the counterculture movement in the 60s and after the patents expired, millions saw LSD as means to expand their spiritual horizons. Although soon after there was a cultural and literal crackdown on any sort of drug and LSD became illegal in 1968. Since its illegalization it has become very difficult to study it because of legal restrictions. In Australia LSD is schedule 9 (S9) meaning it is a prohibited substance and in the United States it is still classified by the Drug Enforcement Administration as a Schedule I drug, cataloguing it as one of the 'most dangerous drugs' with 'no currently accepted medical use and a high potential for abuse.'

Hows It Work and How Dangerous is it

[image: ]LSD unlike most other psychoactive drugs is active in the microgram (μg) range, in contrast to majority of other psychoactive drugs which are chemically similar like psilocybin dimethyltryptamine, however are active in the milligram range (mg). LSD affects various brain receptors such as the dopamine receptors, adrenergic receptors, and glutamate receptors with majority of research conducted is on the stimulatory serotonin receptor 5-HT2A. The above illustration in figure 1 shows a part of the 5-HT2A serotonin receptor. The light blue section is representative of the binding state of the receptor whilst the dark blue section is representative of the lid. LSD hits the receptor at an unexpected angle causing the lid to fold over the LSD and “trap” it in the receptor. It is this phenomenon which causes the elongated “trips” that are associated with LSD lasting in excess of 12 hours. The hallucination is caused as the LSD remains trapped resulting in continual firing of receptor. Clare Stanford, a psychopharmacologist at University College London hypothesises that 'serotonin helps keep a handle on perception and actually stops us from hallucinating.' So by blocking the serotonin receptors in your brain with psychedelics such as LSD, your brain loses its grip on perception and thus you hallucinate. Or another idea, which is presented by Andrew Sewell, a Yale psychiatrist who studies psychedelic drugs, is that LSD enhances some part of your perception and that such drugs lower activity to the thalamus. It sits in the center of your brain and filters your sensory information from all your nerves. Sewell thinks that by dampening down this filter, you become more aware of the information actually coming into your system like sights and sounds becoming louder or brighter, and by seeing things you have never noticed before. Or you might just start seeing things period. Recently, LSD research has seen a revival and using contemporary neural imaging techniques, researchers found that the drug causes parts of your brain to communicate in unique ways, especially in the visual cortex potentially explaining the vivid and complex hallucinations There's also decreased blood flow in the default mode network, correlating to strong changes in consciousness, characterized as ego-dissolution, described as a feeling where the boundary that separates you from the rest of the world dissolves. Many people report this feeling brings a sense of reconnection with themselves, others, and the natural world. In fact, a study on 20 healthy volunteers receiving 75μg of LSD saw that 2 weeks after being dosed, they scored higher for the traits of optimism and openness, with increased creativity and imagination. This has led researchers to consider LSD as a therapy for patients with death anxiety and life-threatening illnesses. Researchers found that 12 months after treatment, patients reported a reduction in anxiety and rise in quality of life, as the drug helped them restructure their habits and worldview. It is also why the trend of micro dosing has emerged; this is where a person takes a sub-perceptual dose of LSD about 15μg. This dosage does not induce hallucinations but allegedly results in heightened alertness, energy, and creativity as well as increased productivity and reduced anxiety. LSD is non-addictive and researchers rate it as significantly less dangerous than other drugs such as cocaine, heroin, MDMA, and alcohol see figure 2 and 3 below. A study, published in the journal Lancet also lists LSD as one of the least harmful drugs, both to the user and to others. Another study published in the journal Psychopharmacology found that there’s no link between LSD and mental illness, and in fact it might be beneficial for those who suffer from depression.Figure 1. A part of the serotonin receptor 5-HT2A that binds LSD. (Left) Closed form. (Right) Open form.

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Figure 2

Figure 3 Harm Caused by Drugs

Despite this there's still a large lack of scientific studies on LSD to the explain the widespread micro dosing trend and use in general. Even experienced hallucinogen users sometimes experience “bad trips” which in severe cases can cause both temporary and long-lasting irrational fears, paranoia, and panic attacks. LSD can also cause flashbacks, where months after the drug has worn off, it can feel as if the user is experiencing the effects of the compound all over again. In some extreme occasions, people have developed Hallucinogen Persisting Perception Disorder (HPPD), which is described as “a never-ending trip”. But one study published in the journal of Drug and Alcohol dependence concluded that such flashbacks or HPPD, is incredibly rare. The notion that LSD can lead to psychosis and the risk of suicide are also overstated. The 14% of participants in the US national survey who had done psychedelics in their life had no increased risk of developing psychosis, depression, or suicide attempts, but the new research around LSD's potential positive effects is also very new, so if anything is clear it is that more research is needed on this drug.

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