The World of Psychedelics

May 2024

Researcher: Kiana Danesh

Editor: Neha Chowdhury

Hallucinogens, also referred to as psychedelic drugs, are a class of recreational drugs that strongly alter a person's cognitive function, perception, and senses. Psychedelics are not considered addictive, but they can hook a person on the sensations they produce. All psychedelics come from a primary pharmacophore and are known for their high brain penetrance and relatively high affinity. Even though psychedelics are listed as Schedule I drugs under US law, they are still used predominantly in spiritual practices.

As mentioned before, although psychedelics do not cause physical dependence, they can still hook a person on the effects they produce. This could lead to substance-use disorders. A rare consequence caused by the abuse of psychedelics is called Hallucinogen Persisting Perception Disorder (HPPD). People who suffer from this disorder have had past experiences with hallucinogens but continue to experience warps in perception and time for months and years after usage. Persons also experience short-lived “Flashbacks” where the person experiences feelings of detachment and frequent intense visual hallucinations.

Psychedelics are partial or full serotonin receptor agonists, which help them induce their effects. Their chemical structure helps them stimulate and bind to the 5HT2A (5HT = 5-hydroxytryptamine) receptor, which has been found to play a substantial role in causing the neuropsychological effects induced by hallucinogens. The 5HT2A receptor is one of the 15 serotonin receptors found in the brain and is found in high density in the frontal cortex and limbic system. Serotonin receptors are G-protein-coupled receptors (GPCRs) and influence a vast amount of neurological and biological functions, such as mood and memory, and also regulate the release of different neurotransmitters. When a serotonin agonist such as psilocybin binds to a 5HT2A receptor, it triggers the activation of intercellular signaling pathways and complex biochemical processes which, as a result, disrupts the messaging in the brain and disrupts the function of the default mode network, i.e., a set of regions in the brain that are more active when we are performing passive tasks. The default mode network is believed to contribute to the thinking of the future and mind-wandering, which is considered essential for everyday consciousness. This disruption and activation of the 5HT2A receptor induced by psilocin as well as other psychedelics is thought to be an important part of their ability to alter perception and consciousness.

Psychedelic drugs have also been a point of interest for the pharmacology world, especially in treating mental illnesses such as Post-Traumatic Stress Disorder (PTSD) and depression. Research has shown that psychedelics may potentially be a better alternative to antidepressants used in the modern age. Lysergic Acid Diethylamide (LSD) has shown its potency in reducing anxiety. This was observed by Gasser et al. in their study involving 12 patients with anxiety associated with life-threatening diseases. These patients were recruited and had drug-free psychotherapy lessons followed by psychotherapy including the use of LSD 2-3 weeks apart. Some participants had received 200mg of LSD (an experimental dose), while others had received only 20mg of LSD (an active placebo). The experimental dose group had a significant reduction in anxiety, with participants in the experimental dose group reporting lower levels of anxiety than the participants with the active placebo. Both groups did not have any severe adverse reactions, such as panic attacks or suicidal states. The only adverse reactions were changes in heart rate and blood pressure, but this did not affect the trial in any way. This trial shows the potential for psychedelics in the psychiatric world, and the need for more investigations into the matter.

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