20.02.2021 |

Episode #10 of the course Introduction to drugs and behavior by Dr. Daniel McGrath


In this final lecture of the course, we will be discussing some of the commonly used hallucinogens. “Tune in, turn on, drop out”, is the famous saying coined by Timothy Leary, a Harvard University professor who was a counter-culture icon in the 1960s. Leary, along with colleague Richard Alpert, were strong proponents of the potential that hallucinogenic drugs had for humanity. In the early 60s, they started a research program examining the effects of lysergic acid diethylamide (LSD) and psilocybin (also known as magic mushrooms) on cognition, behavior, and treating mental illness. At that time, hallucinogens were not yet outlawed, and potential negative side effects were poorly understood. The two researchers were criticized for their poorly conducted studies, as well as their frequent self-experimentation, and both were eventually fired from Harvard. Despite this, Leary went on to become an influential figure in pop culture.

As a class of drugs, hallucinogens are quite unique and varied. Also referred to as psychedelics, some are naturally occurring, whereas most are synthesized in a laboratory. Although each drug in this class has somewhat unique effects, they all share the common feature of producing intense sensory and perceptual distortions.

Mescaline and psilocybin are commonly used drugs that are derived from plants. Mescaline, also known as peyote, is harvested from a cactus found in Mexico and parts of the United States. It is often dried and chewed or can be swallowed or mixed with a drink. Psilocybin is a chemical compound found in several species of “magic mushrooms” that grow in a number of countries. The mushrooms can be swallowed, mixed in food, or consumed as a tea.

Lysergic acid diethylamide (LSD), often called acid, is likely the most discussed drug in this class. In 1938, a Swiss chemist named Albert Hoffmann was designing a compound using ergot, which is a fungus found on grains. His goal was to create a medication to stimulate the circulatory system. Initially, the drug was abandoned but eventually re-examined a few years later. It was then that Hoffman discovered the drug’s hallucinogenic properties. As an illicit drug created in illegal labs, LSD is usually sold in small squares cut from blotting paper that has been soaked in liquid. It can also be found as a tablet or gel tab. LSD is administered orally in very small doses, usually takes effect in about 60 minutes, and can last for six to eight hours.

In the brain, LSD is a selective agonist for a specific serotonin receptor called 5-HT2A. Serotonin is a neurotransmitter that plays an important role in regulating mood, perception, and cognition. This is the neurochemical targeted with antidepressants such as SSRIs. LSD has a high affinity for this serotonin receptor and mimics the neurotransmitter. The result is that using LSD leads to immense alterations in perception, hallucinations, mood swings, and physical symptoms like a rapid heartbeat.

Acute effects. Psychedelics cause mind-bending sensory perceptions that are unpredictable and intense. Vivid colors, shapes, sounds are included in the traditional “acid trip”. Perhaps unsurprisingly, neuroimaging research indicates that LSD enhances connectivity between the brain’s visual cortex and other regions during an acid trip. While users will often describe these sensations as being enlightening, this isn’t always the case. Instead, a “bad trip” can involve terrifying hallucinations. This is where the real danger is with LSD use. Overdosing on LSD is not fatal per se; however, the altered sense of reality puts people in real danger of accidents, legal problems, and even suicide. For example, there have been reports of people on LSD jumping out of windows believing that they could fly. As it takes several hours for the effects to wear off, this represents a real danger for some users.

Chronic effects. LSD does have some concerning long-term health effects. Regular use can cause alterations in the brain’s serotonin system, leading to disruptions in mood and the ability to experience pleasure from other things in life. Some people also report having ‘flashbacks’. This describes unexpectedly experiencing the effects of an acid trip weeks over even years after use. Lastly, for a small number of users, these flashbacks could be a sign of hallucinogen persisting perception disorder (HPPD). With HPPD, hallucinations and alterations in perception are longer lasting and more problematic to their daily functioning. Fortunately, HPPD will often resolve on its own.

Addiction potential. Tolerance to LSD, as well as psilocybin, occurs very quickly. If someone uses LSD for several days in a row, they will no longer be able to achieve the same psychedelic state. However, a few days after they stop using the drug, tolerance will quickly fade, and the drug will once again achieve its full potency. Ultimately, this means that unlike other drugs, people who use LSD do not need to continually increase their dose. In addition, LSD does not alter dopamine transmission in the reward center in the way that other drugs do. As such, LSD doesn’t lead to physical dependence and addiction in the traditional sense. That said, there are people who will be long-term users of the drug.

Finally, psychedelics are now experiencing a bit of a renaissance in the research community. New interest in their therapeutic value has led to research on using some hallucinogens for the treatment of psychiatric disorders and substance use disorders.

Congratulations! You have reached the end of this Highbrow course on drugs and behavior. I really hoped that you enjoyed it and now have a greater understanding of how drugs interact with our psychology.


Recommended book

LSD My Problem Child: Reflections on Sacred Drugs, Mysticism and Science by Albert Hoffmann


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