Will Magic Mushrooms Cure My Depression?

Rachel Biggs
May 04, 2022
Mystical fly agarics glow in a mysterious dark forest. Fairytale background.
Licensed from istockphoto.com

Just don’t be sad. This was “advice” that I actually received from someone once about my depression. I wasn’t just sad – I was numb. I was so physically exhausted that I couldn’t get out of bed, and was unable to sleep at night. Food had no taste, so I just didn’t eat. My body was deteriorating and I couldn’t even find the energy to care.

Each year, approximately 20% of American adults suffer from a mental illness causing an economic burden of hundreds of billions of dollars per year – a cost shared by patients and the healthcare system. Treatment of mental illness has progressed significantly in the 21st century; however, current treatments, including monoamine oxidase inhibitors (MAOIs), tricyclics, and selective-serotonin reuptake inhibitors (SSRIs), have many issues that make taking these medications difficult, including slow onset, low efficacy, extremely uncomfortable side effects (i.e., dizziness, headaches, issues sleeping, stomach aches, etc.)­, and the need to take a pill every day.

Furthermore, finding the right medication with the correct dosage can be extremely challenging, and after many visits with a psychiatrist, some suffering with a mental illness may never find a treatment that works for them. 

"Overall, the use of psychedelics seems to be an efficacious treatment for many mental health disorders."
-- Rachel Biggs

Recently, buzz about a new class of therapeutics for treating mental illness has been building. Psychedelic drugs have been reported to have broad therapeutic potential, demonstrating efficacy for treating depression, post-traumatic stress disorder (PTSD), anxiety disorder, substance abuse disorder, and many others.

Psychedelics have been used for centuries by indigenous peoples around the world in ceremonies for emotional, physical, and spiritual healing. These drugs belong to a more general class of compounds known as psychoplastogens.

There are three categories of psychoplastogens: dissociatives, like ketamine; hallucinogens, like psilocybin, N, N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD); and entactogens, like 3, 4-methylenedioxymethamphetamine (MDMA). Psychoplastogens robustly promote structural and functional neuroplasticity in key circuits relevant to brain health, and unlike traditional antidepressant drugs, they are seen to produce fast-acting and sustained beneficial effects after only a single administration.

One of the oldest and most widely known theories in the field of psychology is that the development of neuropsychiatric diseases results from chemical imbalances in the brain. This belief was supported by the discovery that depletion of monoamine levels (a class of neurotransmitters that includes serotonin, dopamine, and epinephrine) in the brain can cause depressive symptoms. Further support came from the fact that compounds that elevate monoamine levels (current standard of care drugs like MAOIs) seemed to alleviate depressive symptoms.

However, several new pieces of evidence suggest that the chemical imbalance hypothesis is a drastic oversimplification of how mental illness truly manifests. Chronic administration of SSRIs leads to changes in structural neuroplasticity that are positively correlated with their therapeutic effects. This means that these drugs work to treat mental illness only after chronic administration causes changes in brain structure.

Induced plasticity has been hypothesized to play a role in the actions of essentially all antidepressant treatments (slow-acting traditional antidepressants, transcranial magnetic stimulation, exercise, etc.), and has led to the development of the neuroplasticity hypothesis – a conceptual framework for understanding mental illnesses as disorders of neural circuits induced by a combination of genetic and environmental factors.

Depression and related neuropsychiatric disorders are often viewed as stress related illnesses that are exacerbated by chronic stress. It has been seen in animal studies that chronic stress results in atrophy and functional impairment of the prefrontal cortex (PFC). Since the PFC is important for cognition and mediating control over other brain regions, changes in the PFC can be associated with deficits in learning/memory, mood, motivation, and reward seeking – symptoms that are associated with depression and related disorders.

It has been observed in imaging studies that next generation psychoplastogenic antidepressants, like psilocybin and ketamine, are able to increase PFC activation after a single dose. The broad therapeutic utility of these drugs likely arises from increasing PFC activation, as the PFC is a key hub impacted in most neuropsychiatric disorders. 

"The ability to harness the mental healing powers of psychedelics inspires new hope to those with mental health disorders – there could be a cure that doesn’t require a daily pill."

-- Rachel Biggs

While psychoplastogens sound like new miracle drugs for the treatment of mental health disorders, there are still significant barriers to treatment. The costs associated with using psychedelic drugs in the clinic are extremely high. For example, an initial month of ketamine treatment can cost between $4,720 and $6,785 and subsequent months can cost between $2,360 and $3,540. Treatment with psilocybin can be even more expensive because the treatment needs to be done in a clinical setting in the presence of two licensed therapists monitoring the patient for the entirety of the experience, which can last 6-8 hours. It is a concern that these paradigm shifting drugs will only be available to those who can pay for them, which would not address the overall burden of mental health in the U.S.

Another barrier is that some people may not be willing to take a hallucinogenic compound because acute anxiety and challenging experiences are possible, along with the social stigma against “getting high” that many people subscribe to. There is evidence that people can still benefit from ketamine treatment without experiencing the dissociative phenomenon associated with it.

There is potential for non-hallucinogenic psychoplastogens to alleviate symptoms of mental illness. However, many patients describe the psychedelic-induced “peak” or “mystical experiences” associated with these drugs to be extremely meaningful, and that the intensity of these events correlates with therapeutic responses. Direct comparisons between hallucinogenic and non-hallucinogenic psychoplastogens must be conducted to truly understand if changes in neurocircuitry are responsible for the underlying efficacy of these treatments. It is possible that the “mystical experience” or revelations that occur with use of the hallucinogenic compounds also contributes to their astounding positive effects.

Overall, the use of psychedelics seems to be an efficacious treatment for many mental health disorders. More research on non-hallucinogenic versions of these drugs must be done to lessen the financial burden of treatment, increase patient willingness to receive treatment, and ensure that these compounds would have the same lasting effects as the original hallucinogenic types. The ability to harness the mental healing powers of psychedelics inspires new hope to those with mental health disorders – there could be a cure that doesn’t require a daily pill. 

For me, treatment was difficult. Taking a pill every day with multiple side effects was just something I had to live with, and it definitely helped me get to a better place. However, finding the right medication and dosage was exhausting and I wanted to give up. Each one had a different problem and the “right” pill was just the one that was most tolerable, not the most comfortable. Psychedelic treatment has not only shown improvement in patients, but it comes without these horrible side effects, which would probably lead to many more people having successful outcomes. If the doctor had offered me mushrooms, I would’ve taken them.