Could Tripping on Shrooms Solve Depression?

In this article, we will explore the history of hallucinogens, understand the mechanism of these drugs in the brain, and what potential they have as a medical treatment.

What is a Hallucinogen?

Wave Fractal Vision Art  - fsm_t1 / Pixabay
fsm_t1 / Pixabay

A hallucinogen is a drug that causes hallucinations, which are sensations and imagery that seems real but are not. There are two categories: Classic and Dissociative. Classic hallucinogens cause typical hallucinations whereas Dissociative hallucinogens cause the user to feel disconnected from their body.  

Most people associate this group of chemicals with drugs but humans have actually created some of them as medicines.

In the 1940s the discovery of LSD led to the development of the drug as a treatment for mental illnesses. In the 1960s, abuse of the drug and stigmatization put psychedelics on the Controlled Substances Act drug list. This really limited the possibility of further research. 

Hallucinogens were used by early cultures and they played a large role in religion and spirituality. Below are common hallucinogens and a bit of information about them:

Classic Hallucinogens

  • LSD – Lysergic acid diethylamide is one of most powerful hallucinogens and is very famous. Also known as acid.
  • Psilocybin – Comes from mushrooms and is also known as magic mushrooms/shrooms.
  • Peyote – A substance that comes from a cactus but can also be synthetic.
  • DMT – A chemical found in plants that can be used to make tea. It can also be made in a lab and is usually smoked.

Dissociative Drugs

  • PCP – Developed in the 1950s as a general anesthetic for surgery. It is no longer used due to serious side effects. It can be found in various forms and is sometimes referred to as Angel Dust, Hog, Love Boat, and Peace Pill.
  • Ketamine – Is used as a surgery anesthetic for humans and animals. Can be sold on the streets as powder and pills but can also be injectable. It can be used as a date rape drug. Also known as Special K and Cat Valium.
  • Dextromethorphan – A cough suppressant in drugs such as Mucinex. It can be a dissociative drug in high doses. Also known as Lean and DXM.
  • Salvia – Comes from a plant and is typically ingested by chewing leaves and drinking the juices. It can also be smoked or vaporized. 
Smoke Human Alone Weird Drugs  - Free-Photos / Pixabay
Free-Photos / Pixabay

What Do We Know About These Drugs

We know that these drugs alter the brain, specifically:

  • Mood 
  • Thought processes
  • Perception
  • Experience of the self
  • And more

About The Brain

Brain Anatomy Physiology Human  - OpenClipart-Vectors / Pixabay
OpenClipart-Vectors / Pixabay

The Anatomy of The Neuron

Neurons are the type of cell used in the brain and in the nerves. They are long skinny cells, where the thin skinny body is called the axon. On one end they have a head with a nucleus. On that same end there’s a bunch of little fibers coming off like roots of a tree. These are dendrites and they feel around to make connections with other neurons. These dendrites connect to the tail end of another neuron. This is the axon terminal. The dendrites and axon terminals arrange really close together but leave a bit of space. This joint is called a synapse. Neurons communicate by sending chemicals across the synapse. The release of these chemicals is triggered by an electrical impulse.


These are the chemical messages being sent between neurons. They trigger different mechanisms and those mechanisms do different things. Here’s a list of 7 common neurotransmitters and their mechanism: 

  • Acetylcholine – Plays a large role in the passive portion of the nervous system.
  • Dopamine – Plays a role in motor control, motivation, arousal, reinforcement and reward behavior. Also known as the feel good transmitter. It Is released when we eat and during sex. It contributes to the feelings of pleasure and satisfaction.
  • Gamma aminobutyric acid (GABA) – Is an inhibitory neurotransmitter. It calms neurons down and is known to be released for controlling fear and anxiety.
  • Glutamate – This acts in opposition to GABA. It triggers an excitatory response in these cells. Excessive levels lead to insomnia, concentration problems, mental exhaustion, and low energy
  • Histamine – This is a neuromodulator, which means that it manages the release of other neurotransmitters, moderating their presence. Altered levels of histamine will result in less control over the other neurotransmitters producing a wide range of possible results.
  • Norepinephrine – This acts as a neurotransmitter. It plays an important role in attentiveness, emotions, sleeping, dreaming, and learning. Alterations have been linked to mood disorders such as manic depression.
  • Serotonin – This is another neurotransmitter in the brain. It plays large role in mood, emotion, appetite, digestion, and sleep wake cycle as it has a relationship with melatonin. 
Brain Neuron Nerves Cell Science  - OpenClipart-Vectors / Pixabay
OpenClipart-Vectors / Pixabay

Serotonin and Depression

One explanation for depression is the Serotonin Hypothesis. It is about 50 or so years old, and proposes that diminished serotonin activity plays a minor role in the complex workings of depression. There has been some evidence to show that when we impair serotonin function, it can cause clinical depression in some cases. Clinical depression is the diagnosis of depression, rather than the feeling of depression.

We still explore this hypothesis despite the lack of research evidence. Why? A very common class of drugs called SSRIs, act to increase the levels of serotonin in the brain. This has been shown to help patients with depression. However, we have learned from this. 

It has contributed to our understanding of how serotonin influences mood in depressed patients. It is implied by the response of patients taking SSRIs that serotonin influences the way we react to emotional information. Because mood and emotions are not the same, it seems that serotonin does not influence mood but rather emotion, and the reaction to emotional information.

Death Darkness Dark Hood Hooded  - PublicDomainPictures / Pixabay
PublicDomainPictures / Pixabay

Psilocybin, Serotonin, and Depression

Psilocybin is the active ingredient in magic mushrooms. The species of mushroom is Psilocybe cubensis. It has been shown that hallucinogens have high affinity to different neurotransmitter receptors. Affinity is a molecule’s ability to bind to its receptor. Specifically, hallucinogens such as psilocybin correlate best with the serotonin receptor (5-HT).

In knockout 5-HT mice, classical hallucinogens are devoid of activity. Additionally, a study was done where they gave people shrooms and a certain group of them got a 5-HT antagonist, meaning a substance or molecule that binds to the receptor so other things can’t bind. When they did this, those with the antagonist did not have psychedelic effects. This information has shown that psilocybin and similar drugs act on the 5-HT serotonin mechanism. 

In an article published november of 2020, patients with moderate to severe depression got two doses of psilocybin pills, spaced one and a half weeks apart. They also got therapy and support before, during, and after taking the drug. When using a common depression rating scale with a point range between 0-52, 52 being severe depression. Average score in participants before psilocybin was 22.9 dropped to 8.5 only 4 weeks after the second dose. For reference, 7 or less is considered to be no depression.

The issue with serotonin is that it doesn’t pass the Blood Brain Barrier (BBB). Because of this, we have to increase serotonin by rigging another system. Hence the SSRI: Selective Serotonin Reuptake Inhibitor. SSRI’s keep serotonin from being reabsorbed, while more is still released, thus boosting the levels of serotonin.

Psylocibin as a drug would be theoretically successful because it would be similar to giving the brain pure serotonin. Since psilocybin can pass the BBB, it could go to the brain and activate the serotonin receptors, possibly boosting mood and improving reaction to emotional information


Serotonin has been shown to play a part in the disease process of depression. It is implied that diminished serotonin levels contribute to depression. Depression can be improved by increasing serotonin levels and increasing how much serotonin receptors are triggered. 

Psilocybin is a possible option for an antidepressant drug. A recent small study has shown decreased severity in depression 4 weeks after 2 doses of psilocybin. It is clear that more research is needed in the future. There is a barrier to this research though, due to the ethics of human trials. It begs the question, where would we be if hallucinogens were not federally controlled?

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