Psilocybin treatment for PTSD: a Clinical Trial protocol

There have been numerous studies published to date that provide an overwhelming rationale for conducting a Clinical Trial utilizing psilocybin to treat PTSD.  Below is a list of PTSD related issues and the recent research that has provided ample evidence to support such a trial and could function effectively as a key aspect in someone's protocol:

PTSD.  There has been a recent animal model study demonstrating the efficacy of low-dose psilocybin in treating PTSD as well as a 1968 case report on a long-standing chronic pain/depression/PTSD patient treated successfully with psilocybin. The animal model study also demonstrated psilocybin's ability to promote hippocampal neurogenesis.

Depression. A recent Lancet Psychiatry article has shown psilocybin to be highly effective for patients with treatment resistant depression.

No serious or unexpected adverse events occurred during the course of the study and all patients demonstrated a reduction in depression severity at 1 week that was sustained in the majority for 3 months. Eight (67%) of the 12 patients achieved complete remission at 1 week and seven patients (58%) continued to meet criteria for response at 3 months, with five of these (42%) still in complete remission. This is quite remarkable since the equivalent remission rate for SSRIs is around 20%. Unlike current anti-depression medications, psilocybin does not have to be given daily, perhaps only once or twice as in this study.

Social isolation/exclusion. Numerous studies have demonstrated improvement of social cognition deficits in various psychiatric disorders after psilocybin administration compared to placebo. Furthermore, emotional empathy was enhanced after treatment with psilocybin as well as a decrease in social exclusion and social stigmatization.

Addictions. A recent pilot study  involving 15 psychiatrically healthy nicotine-dependent smokers (10 males; mean age of 51 years), with a mean of six previous lifetime quit attempts, and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake demonstrated an 80% abstinence at 6-month follow-up. The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and/or pharmacological therapies (typically < 35%).

There are currently three Clinical Trials examining psilocybin's ability to help individuals with addiction related disorders.

Existential distress.  To me, this is key.  Existential distress is, in my opinion, what gives rise to PTSD in the first place. When a Warfighter heads out on patrol day after day not knowing if he will return, this creates a definite existential distress.  Why some develop PTSD as a result of this experience and others do not is not known but I suspect levels of pre-existing systemic inflammation may play a key role. A future study will examine psilocybin's ability to decrease inflammation in the brain.

Two recent studies. one performed at NYU, the other at Johns Hopkins that provided psilocybin to cancer patients with life-threatening in an attempt to mitigate their existential distress will soon be published. Preliminary results have been provided by NYU and by Johns Hopkins.  It is reasonable to infer that what is effective for these patients will be effective for those with PTSD as well.

Anger/violence. A recent study from the Journal of Psychopharmacology looked at 302 men ages 17-40 in the criminal justice system. Of the 56 percent of participants who reported using hallucinogens, only 27 percent were arrested for later IPV as opposed to 42 percent of the group who reported no hallucinogen use being arrested for IPV within seven years.

Dr. Peter Hendricks, one of the study authors, commented that "A body of evidence suggests that substances such as psilocybin may have a range of clinical indications," he said. "Although we're attempting to better understand how or why these substances may be beneficial, one explanation is that they can transform people's lives by providing profoundly meaningful spiritual experiences that highlight what matters most. Often, people are struck by the realization that behaving with compassion and kindness toward others is high on the list of what matters."

Suicidal ideations. Two previous studies have demonstrated psilocybin's potential effectiveness in preventing suicides.  A 2013 article in PLoS One used data from over 130,000 individuals drawn from years 2001 to 2004 of the National Survey on Drug Use and Health and demonstrated no significant associations between lifetime use of any psychedelics, lifetime use of specific psychedelics (LSD, psilocybin, mescaline, peyote), or past year use of LSD and increased rate of any of the mental health outcomes. Rather, in several cases psychedelic use was associated with lower rate of mental health problems to include suicide.

A 2015 article from the Journal of Psychopharmacology by researchers from the University of Alabama and Johns Hopkins demonstrated lifetime classic psychedelic use was associated with a significantly reduced odds of past month psychological distress (weighted odds ratio (OR)=0.81 (0.72-0.91)), past year suicidal thinking (weighted OR=0.86 (0.78-0.94)), past year suicidal planning (weighted OR=0.71 (0.54-0.94)), and past year suicide attempt (weighted OR=0.64 (0.46-0.89)), whereas lifetime illicit use of other drugs was largely associated with an increased likelihood of these outcomes.

Anxiety. Numerous studies have demonstrated a decrease in anxiety in those who have taken psilocybin with the proper Set and Setting. One specific 2011 study from UCLA titled Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer demonstrated a significant reduction in anxiety at 1 and 3 months after treatment as measured by the State-Trait Anxiety Inventory and the Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months in 12 adults with advanced-stage cancer and anxiety.

In conclusion, with the possible exception of Ayahuasca, there exists no other known compound that has shown effectiveness with all the various issues manifested in those afflicted by PTSD.  It is less toxic than caffeine, not addicting and has to be given only once or twice. This is an excellent opportunity for the DoD and/or VA to conduct a Clinical Trial utilizing psilocybin to treat PTSD in an attempt to decrease suicides in active duty military and veterans, to take whatever steps necessary to find the best treatment for this debilitating condition.

Psilocybin shows great promise for those with treatment resistant depression

The World Health Organization describes depression as "the leading cause of disability worldwide" afflicting over 350 million people globally and costing the U.S. more than $200 billion annually which makes the promising research published 17 May 2016 in Lancet Psychiatry extremely timely and relevant. The news media has taken notice as well.

The Lancet Psychiatry article titled 'Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study'  (PDF) by researchers at the Imperial College London, ranked as a top 10 Univesity globally, was a pilot study which involved 12 patients, all whom had a failed response to standard medications and had suffered with major depression for an average of an astounding 17.8 years.

Patients received two doses of psilocybin (10 mg and 25 mg, orally, 7 days apart) in a supportive setting with psychological support provided before, during, and after each session if needed.  The psilocybin utilized in the study was synthetic, no actual mushrooms were consumed in order to provide a known amount of psilocybin for each patient. fMRI data was collected but will be detailed at a later date.

Since this was a feasibility trial, there was no control group.  However, since these patients had tried various other medications over time, this may be considered an 'N of 1' study with the patients serving as their own controls.

No serious or unexpected adverse events occurred during the course of the study and all patients showed some reduction in depression severity at 1 week that was sustained in the majority for 3 months. Eight (67%) of the 12 patients achieved complete remission at 1 week and seven patients (58%) continued to meet criteria for response at 3 months, with five of these (42%) still in complete remission. This is quite remarkable since the equivalent remission rate for SSRIs is around 20%. Unlike current anti-depression medications, psilocybin does not have to be given daily, perhaps only once or twice as in this study.

Marked and sustained improvements in anxiety and anhedonia were also noted. The researchers are now planning a larger randomized controlled trial as the next stage of this promising research. The inclusion of concurrent sessions of cognitive behavioral therapy or mindfulness meditation for some weeks or months during and following psilocybin administration may assist patient with the integration of what they learned during their 'trip treatment'.

Unfortunately the researchers ran into a ridiculous amount of legal red tape which took 32 months between having the grant awarded and treating the first patient since psilocybin is categorized as a Class A illegal drug in the United Kingdom (Schedule I in the United States). In a previous post, I have detailed the rationale for why psilocybin should not be classified as a Schedule I drug. As a brief refresher, the criteria for a compound being listed as Schedule I are:

1. The drug or other substance has a high potential for abuse. Comment: not true for psilocybin. It has shown promising in treating those with substance abuse issues.
2. The drug or other substance has no currently accepted medical use in treatment in the United States. Comment: not true for psilocybin. It is being used by many already but they have to take chances and go it alone without proper medical/spiritual supervision.
3. There is a lack of accepted safety for use of the drug or other substance under medical supervision. Comment: not true for psilocybin. There have been no serious adverse events in the hundreds of patients who have recently taken psilocybin in Clinical Trials.
4. (Unofficial) Because we said so!  Comment: this is the only reason psilocybin is listed as Schedule I as none of the 3 Official criteria are based on rational scientific thought. The reason psilocybin was made and remains Schedule I is purely political. While not a strong advocate of medical marijuana, I do applaud the DEA for currently reconsidering removing it from Schedule I status which will allow the needed research to proceed with less regulatory hurdles. Hopefully they will soon reconsider psilocybin as well. With the billions of dollars at stake, there will be an unprecedented amount of pressure on the DEA not to move psilocybin off of Schedule I status.

Senior author and Neuropsychopharmacologist Dr. David Nutt expressed reasonable displeasure over the 32 month bureaucratic delay stating “Every interaction — applying for licenses, waiting for licenses, receiving the licenses, applying for contracts for drug manufacture, on and on — involved a delay of up to two months. It was enormously frustrating, and most of it was unnecessary,” says Nutt. “The study result isn’t the remarkable part — it’s the fact that we did it at all.”

A thoughtful Commentary (PDF) in Lancet Psychiatry by Dr. Phil Cowen, a depression researcher with the University of Oxford, accompanies the research.

The VA and/or DoD has a primary responsibility towards their patients with PTSD and it is very disconcerting that they are not taking the lead in this very promising research.  Depression and PTSD go hand in hand as the statement below from the Veterans Administration points out:

Many symptoms of depression overlap with the symptoms of PTSD. For example, with both depression and PTSD, you may have trouble sleeping or keeping your mind focused. You may not feel pleasure or interest in things you used to enjoy. You may not want to be with other people as much. Both PTSD and depression may involve greater irritability. It is quite possible to have both depression and PTSD at the same time.

So, lets get going!