Tom Palmer explains the history of Lysergic Acid Diethylamide

The most common use for LSD (Lysergic Acid Diethylamide) in today’s society is for recreational exploitation, a habit that started in the 1960s after being used for psychological means as early as the 1940s. It was during this period of abuse that its use spread to the United Kingdom, where to this day its consumption is much higher than the worldwide average.

The science behind LSD and the hallucinations it causes is a relatively new topic to researchers. It binds to the D₂ receptors, a receptor for dopamine, and all serotonin receptors apart from two. Serotonin and dopamine are both examples of monoamine neurotransmitters, a type of chemical messenger in the body, with serotonin being responsible for modulating mood, reward, cognition and memory, and dopamine controlling pleasure. Although, while being seen as the main chemical of happiness and pleasure, dopamine is now more thought to control motivation and the desirability of an outcome.

Depending on the receptor it binds to, dopamine either increases or decreases the amount of cAMP (cyclic Adenosine Monophosphate), another chemical messenger. This transfers the effects of certain hormones into the cell which can’t pass through the membrane, such as adrenaline and glucagon. It is also involved in the activation of protein kinases, enzymes that modify proteins to change their function. The receptor that LSD binds to, D₂-like receptors, inhibit the production of cAMP, effectively slowing your brain down, reducing some of your function and also some passive immune response. An equal mix of D₁ and D₂ receptors in the brain is needed for dopamine to exert its full effects, but LSD only binds to one half, toppling the balance of chemicals and messengers in the brain.

Serotonin is the neurotransmitter responsible for regulating mood, feelings of happiness and anxiety. High levels of serotonin result in good moods and joyfulness, while low levels can lead to depression and anxiety. The psychedelic effects of LSD come from cross-activation of certain serotonin receptors, called 5-HT₂ receptors. When these receptors come into contact with serotonin or a few other chemicals, such as some psychedelic or pharmaceutical drugs, they activate an intracellular second messenger cascade. Second messengers facilitated by primary messengers and are most often responsible for activating cellular responses.

LSD binds to the D₂ and 5-HT receptors in the place of dopamine and serotonin, in a way ‘mimicking’ them, and causing the effects that these neurotransmitters would have on the brain but to an extreme extent. The secondary messenger released when the receptors are in use is most often glutamate. Glutamate is an ion of glutamic acid and is a neurotransmitter like serotonin and dopamine. It is the most common excitatory neurotransmitter in the body, used by every major excitatory function and is involved in up to 90% of all synaptic connections in the brain. The actions of LSD increase the amount of glutamate released in the cerebral cortex, a large layer of tissue in the cerebrum, the largest part of the human brain. The cerebral cortex plays a huge part in the body and brain’s function, most importantly (in this case) perception, awareness, thought and consciousness.

With the increase in glutamate, excitation in this area of the brain also increases. Excitation is when the signalling from one neuron (a nerve cell in the brain) to the next makes the latter cell much more likely to fire (neuron firing is neurons communicating with others by use of neurotransmitters). The excitation of the cerebral cortex takes place in two of its six layers, layers IV and V. These two, layer V especially, are connected with the subcortical regions, which are heavily involved in pleasure and emotion.

Many recreational drugs, including LSD, cocaine, amphetamine and nicotine, all activate DARPP-32 pathways. DARPP-32 (Dopamine-and-cAMP Regulated-Neuronal Phosphoprotein) is a protein that affects and regulates the amounts of dopamine, adenosine and glutamate in the brain. This enhances the recognition of D₂ receptors, leading to them being used more, and therefore increasing the effects that dopamine would have on the brain. It also enhances the signalling in D₂ – 5-HT₂ complexes, linking serotonin and dopamine, which is most likely the main cause of the drug’s psychotic effects.

These combined chemical effects all contribute towards the extremely heightened emotions, both positive and negative, as well as increasing energy and awareness of surroundings. The science behind the hallucinations that the user experiences, however, is not exactly perfect. Brain scanning done by a team at Imperial College London discovered that while on LSD, brain activity became less coordinated in the region known as the default mode network. This network is most active when the brain is in a ‘wakeful rest’ and not focusing on the outside world, such as daydreaming. A lack of coordination in this region reduces the amount of unconscious processing done by the brain. This leads to a lower awareness of surroundings and also affects the visual cortex.

LSD disrupts the rhythm of alpha brainwaves, which contribute to human consciousness, leading to an effect known as ‘ego dissolution’. This is where the user feels detached from themselves but also makes the brain function in a simpler way. The changed rhythm of alpha brainwaves can also result in parts of the brain communicating with each other that usually act separately. A lower coordination in the visual cortex coupled with input from other areas of the brain is one largely accepted theory of what causes hallucinations for the user. Another theory is that the visual cortex is ‘malfunctioning’ with the lower coordination and so it tries to fill in the blanks, essentially making things up to try and cover for the lack of information.

As I mentioned before, the cause of hallucinations is not an exact science, mostly because it barely changes brain activity. This means it is very hard to observe anything occurring in the brain, and any scanning or imaging simply shows the mass of other effects that the drug has on the brain, masking the visual effects.

Overall, LSD mimics dopamine and serotonin to produce the same effects, but 10 times over. It combines multiple techniques to increase pleasure, excitement and energy to the absolute maximum, with the side effect of knocking the user’s visual coordination askew. But it also has its downsides, that I very briefly mentioned before. Although the drug is not known for addiction, there may be unknown side effects and the use of it is discouraged.