CategoriesMicrodosing Mushrooms for Depression

Microdosing Mushrooms and Depression

Today, I’m talking about Psilocybin, also known as magic mushrooms, and how it’s on the fast track as a treatment for treatment-resistant depression. Treatment-resistance occurs when a person’s depression does not resolve with two antidepressant trials. The current options are to add another medication, like an antipsychotic medication. Some of these are medications like Abilify, or Rexulti. A newer medication for this is Spravato, which is Ketamine. We also use anticonvulsant therapy and Transcranial Magnetic Stimulation. Unfortunately, only about 40 to 60% of people get completely better with medication, and for some people, not completely better is tolerable, but for others, you can still feel pretty miserable and have a lot of side effects that you’re dealing with, like weight gain.

What is psilocybin and how does it help depression?

So, new on the scene is Psilocybin. Psilocybin is a compound found in mushrooms that has psychedelic properties. Psychedelic means that it makes you hallucinate. Psilocybin works in the brain by activating the 5HT-2A receptor on the neuron to increase serotonin. It’s been used recreationally for years and is known to broaden your thinking, and relax you, and amplify your emotions.

On this issue of broadening your thinking, there have been studies that have shown that after only two doses of Psilocybin, the person was less neurotic and less authoritarian when it comes to their political views. Neuroticism is a measure of mental vulnerability to anxiety and depression. Authoritarian political views means that you prefer more government control, versus libertarianism, is aligned with freedom from government control.

So, after one to two doses of Psilocybin, people were more mentally flexible and less uptight about things. And the really interesting thing to me about this is that the attitude changes were seen seven to 12 months after those one to two doses. It’s not like they had to continue consuming it daily to maintain this new state of mind.

History of psilocybin

Here’s a little of the history or Psilocybin. The studies on Psilocybin date back as early as the 1950s. This led to the approval of the drug Indocybin, made by Sandoz Pharmaceuticals in 1960. But it only lasted six years on the market before it was banned for abuse. Our society pushed back against the endorsement of a hallucinogenic drug. In 1970, Congress passed the comprehensive Drug Abuse Prevention and Control Act, which created a classification of drugs based on their potential for abuse, accepted medical use, and accepted safety under medical supervision. They created five classes called Schedules.

Scheduled drugs, psilocybin, and anti-depressants

Schedule one are drugs that have a high potential for abuse, no known medical use and lack safety data. In 1970, Psilocybin and LSD were put in this category. These drugs can only be used for investigational purposes. Schedules Two through Five include drugs that have medical use but still have a high potential for abuse. And the lower the number, the higher the abuse potential.

So, for example, Schedule Two drugs include opioids like Oxycodone, and stimulants like Adderall. Schedule Three includes ketamine and benzodiazepines, like Klonopin and Xanax. Schedule Four includes sleeping medications, like Ambien. Schedule Five includes drugs that have the lowest potential for abuse or dependence. And some examples of drugs on this schedule are Lyrica, Lomotil, which is a diarrhea medication, and some cough preparations that contain Codeine. Drugs that are not considered to have any potential for abuse or dependence are not put on a schedule.

So, not all medications are scheduled drugs. Antidepressants are examples of medications that are not scheduled controlled substances. So, back to Psilocybin. A renewed interest in Psilocybin began in the 1990s and these studies showed therapeutic benefit for people suffering from anxiety, depression, and alcohol dependence. Many of these studies used one to two doses of Psilocybin called Microdosing.

New drugs, new studies that deal with depression

These small studies have accumulated over time, gaining the attention of large companies wanting to develop the drug for medical use. The early results have been so promising that the FDA granted breakthrough therapy designation for Psilocybin. Breakthrough therapy designation allows for a faster track for drugs to be developed and approved for treatment.

The same thing happened with S-Ketamine, marketed as Spravato for treatment-resistant depression. You may be wondering, how long should it now take that it’s on the fast track? That depends on how long it takes for the trials. Spravato was granted breakthrough designation in August 2016, and it was approved to be used as a drug for treatment-resistant depression in March 2019. That’s two and a half years, which seems like a long time, but on average, it takes about 10 years or more for a drug to go from phase one clinical trials to FDA approval.

So, drugs that show some previous evidence that it can treat a life-threatening illness can be pushed through the system faster so that they can get to market quicker. There’s a real race to get this to market.

The FDA granted breakthrough therapy designation in 2018 to Compass Pathways for treatment-resistant depression using a range of doses. Then, in November 2019, the FDA granted the designation to a company, Usona Institute, to treat regular depression, not treatment-resistant, using a single dose.

One dose, and you’re good for months? That would be amazing.

Let's talk about bi-polar and depression

One thing I want to mention is when it comes to bipolar disorder. Depression inside of bipolar disorder is different from unipolar depression. Psylocybin is being studied for the treatment of unipolar depression. We don’t know what effect it will have on possibly treating or triggering mania or psychosis.

And this doesn’t mean that it can’t help with the depression that comes with bipolar disorder, but we’ll first have to see what side effects are associated with the drug once they’ve completed the trials, to be able to anticipate how it can affect bipolar disorder. And even though we don’t have a good feel yet for the side effects and safety issues, I’m thinking that they’re likely to be minimal because of the microdosing. That’s a limited exposure, which should produce limited negative effects. So, this is exciting.

– Dr. Tracey Marks, psychiatrist.

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