Psychiatric Applications of Psilocybin

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Photo Credit Fungi Steve

Psilocybin is a member of the tryptamine class of hallucinogens. It is the active compound found in dozens of mushroom species and is responsible for the typical features associated with “shroom” or “magic mushroom” ingestion. Classic effects of psilocybin ingestion are similar to LSD, and include:

week6-psilocybin

 

  1. Oceanic boundlessness: the experience of unity while also being boundless
  2. Visionary restructuralization: auditory and visual distortions and hallucinations

These effects, while each fascinating in their own right, are not the topic of today’s post. Rather today, we’re going to focus on psilocybin’s antidepressant effects.

Psilocybin acts directly on serotonin 5HT-2A receptors. Interestingly, blocking, or antagonizing these receptors leads to improvements in parkinson’s disease-induced psychosis (discussed in a separate blog post here). Psilocybin, acting as an agonist at this same site, appears to have potent antidepressant effects.

Research on psilocybin has shown promise in the treatment of end of life anxiety, obsessive compulsive disorder, and smoking and alcohol dependence. A study from 2008 showed that 14 months after a single dose of psilocybin, greater than half of the participants continued to report an increased sense of wellbeing. Now, in a recent article published in the Lancet, psilocybin has demonstrated preliminary efficacy in the treatment of unipolar (i.e. not bipolar) depression.

Twelve patients (6 women and 6 men) with treatment resistant depression were dosed with two oral doses of psilocybin (10mg and 25mg) 7 days apart. Typical recreational doses of psilocybin range from 10-50mg (i.e. 1-2 grams of dried mushrooms, or 20-30 grams of fresh mushrooms). The participants were dosed in pre-decorated (i.e. low lighting) rooms with music playing through high quality speakers. Patients had psychiatrists sit on either side of them and perform psychological support in the form of check-ins, making sure that the patient experienced a mostly uninterrupted “inner journey.”

Incredibly, at one week and at three months depressive symptoms were markedly reduced. Although clearly not a placebo controlled trial, this study demonstrates significant promise for the future of psilocybin as a treatment for depression and may offer hope for those with treatment resistant depression.

Supplements for Depression

As a psychiatrist in LA, I’m always looking for novel techniques and other ways to help my patients. I recently became aware of a meta-analysis published in the American Journal of Psychiatry that showed great promise for Vitamin D, Omega 3 (fish oil), Methylfolate, and S-adenosylmethionine (SAMe) as adjunctive treatments for depression in patient’s already receiving antidepressants.

Many people take multivitamins and cite reasons like “health” but have no idea what the effects could be. These four supplements could actually help improve your depression. In the meta-analysis the only cited adverse effect was minimal digestive upset.

So, let’s talk about each one individually.

First off, vitamin D. We should probably all be taking vitamin D because 1) we know it serves an important role immune function 2) it is required for proper mineralization of bones 3) it may help prevent falls in the elderly and 4)there are very few (if any) side effects. Now, there is new evidence that vitamin D may help treat depression in depressed patients.  To quote the study, the results were positive and significant. A reasonable starting dose? 1000-2000 IU/day. I personally take 2000IU daily.

Second, Omega 3, or fish oil. Omega 3 is another one we should probably all be taking because it positively impacts cardiovascular risk factors through a myriad of methods including acting as an antiarrhythmic, lowering the heart rate, lowering blood pressure, preventing clot formation, and decreasing the level of triglycerides in your blood. This meta-analysis reveals that there is new evidence for a fish oil as adjunctive treatment for depression. A reasonable starting dose would have a combination of EPA&DHA approximating 1gm. This is the brand and formulation I buy.

Last but not least, methylfolate and SAMe. The evidence for taking these without depression is less robust. Both are participants in essential chemical reactions that happen in your body constantly and a deficiency in folate (related to methylfolate) causes anemia. Both showed positive effects when used as augmentation for antidepressant treatment.

The take home? Vitamin D and Fish Oil are rockstars with few to no side effects. This new meta-analysis only further serves to reinforce that these should both be prominent in your diet, either through naturally-occurring sources or as a high-quality supplement.

Article after the jump: Link

Inflammation, Depression, and … Statins?

There are multiple theories regarding the pathophysiology of depression. The most common (and the one you’ve probably heard about) is the monoamine hypothesis. This theory posits that depression is an imbalance (or depletion) of certain key neurotransmitters in the brain. The imbalance of these key neurotransmitters, namely dopamine, serotonin, and norepinephrine, is believed to cause depression. As such, most common antidepressants fit into classes that limit the uptake and/or breakdown of serotonin (SSRIs), serotonin and norepinephrine (SNRIs and TCAs), or serotonin, norepinephrine, and dopamine (MAOIs).

Today, we’re interested in a different hypothesis involving inflammatory proteins called cytokines. Cytokines are increased within our body when we are having an immune response and with inflammation in general. In patients with depression, certain cytokines have been found to be elevated before treatment (associated with a pro-inflammatory state) and decreased after treatment 1. This implies that cytokines and other inflammatory molecules may cause a pro-inflammatory state that causes our brain to be “inflamed,” thus causing depression. If there were a way to decrease inflammation in our body, perhaps depressive symptoms would improve as well.

On to statins. Statins (think Lipitor, Crestor) are commonly prescribed to treat high cholesterol. Incidentally, they are also believed to have anti-inflammatory properties. This is believed to be the reason why statins decrease the risk for stroke and heart attack independent of their cholesterol lowering effect.

A recent study in Denmark followed 872,216 SSRI users (of whom 113,108 (13.0%) used a statin concomitantly) over the course of 15 years 2. It found that patients who took SSRIs while on a statin had fewer depression-related hospital visits and depression-related hospitalizations. As such, the article concluded that “concomitant treatment with SSRIs and statins resulted in robust advantages compared with SSRIs alone.”

So does this prove the cytokine hypothesis of depression? Should you be taking a statin if you’re depressed? Not quite. Statins are not benign drugs, and the evidence isn’t there yet to recommend augmenting antidepressant treatment with a statin. Regardless, this study represents one more step in the right direction. Here’s to eventually finding a cure (and a satisfying explanation) for the millions of people worldwide who are afflicted with depression.

References:
  1. Cytokines and Depression
  2. Statins and Depression 

A Novel Antipsychotic

For my first blog post I want to talk about… this incredible new antipsychotic that just came on the market. I realize this is a bit esoteric (and random), but I’ve been following this medication since I was in my third year of medical school at Georgetown. It has a completely different mechanism of action from other antipsychotics (think Haldol or Abilify) and has fewer movement side effects compared to other antipsychotics.

So, brief review, antipsychotics are a class of medication used to treat psychotic disorders. Most psychotic disorders are believed to result from overactivity of dopamine (a neurotransmitter). Thus, antipsychotics work by blocking the action of dopamine in the brain. The issue? blocking dopamine can cause movement issues and can exacerbate movement disorders. Certain movement disorders are associated with psychosis creating quite the conundrum for physicians trying to help treat the patient’s psychosis but not wanting to make the patient’s movement condition worse.

A hopeful new solution? Pimavanserin. Pimavanserin is a novel type of antipsychotic that works on serotonin (another neurotransmitter) and has shown to have antipsychotic efficacy without the movement side effects. This is great news for people with Parkinson’s Disease, Lewy Body Dementia or even patients with primary psychotic disorders who are prone to movement side effects.

As a third year med student, I remember being so nerdily excited about the possibilities of this antipsychotic.  As a psychiatry intern at UCLA, I’m incredibly excited to be able to live this out.

More after the jump: Link