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!

Magic mushrooms and blueberries: a recipe for treating PTSD

Individuals with PTSD frequently report experiencing social exclusion and social stigmatization. Social isolation will further compound their traumas, whether the nature of their trauma is mental, physical, moral or a combination. Such was especially the case with Veterans returning from the unpopular war in Vietnam.  Unlike the more recent excursion in the Middle East which had much support following the 9/11 atrocities, the Vietnam veterans were subject to significantly more indifference, rejection and criticism.

Now an exciting new study from the University Hospital of Psychiatry Zurich, authors of numerous psilocybin studies and the Institution that gave rise to Carl Jung, whose work had a profound influence on Joseph Campbell, have published an article titled Effects of serotonin 2A/1A receptor stimulation on social exclusion processing (PNAS April 2016).

In their study, the University of Zurich researchers demonstrated that psilocybin had a positive effect on brain regions to include the dorsal anterior cingulate cortex by stimulation of specific serotonin receptors. These findings may be relevant to the normalization of negative social interaction processing in psychiatric disorders characterized by increased rejection sensitivity. Plus this reduction of psychological pain and fear can be of great importance in facilitating the therapist-patient relationship and the psychotherapeutic treatment of formative negative social experiences.

Psilocybin has demonstrated an ability to increase subjective feelings of connection with the environment and other people, which may lead to stronger and more empathetic connections between people. This in turn may help reduce “egocentric bias” and “render negative experiences more bearable,” the authors of the study wrote.

In another recent article (FASEB April 2106) detailed in MedicalXpress and titled Eating blueberries could regulate genetic and biochemical drivers of depression and suicide the benefits of compound(s) in blueberries that help to ameliorate the depression and suicidal tendencies often associated with PTSD is described.  This is good news since available medical treatments offer only limited relief and a Clinical Trial utilizing psilocybin to treat PTSD, which offers the most promise of any known compound, has yet to be initiated.  Johns Hopkins, this is in your ballpark.  Time to hit a homerun.

The researchers from Louisiana State University (LSU), working with animal models, have found that eating blueberries could help to reduce the genetic and biochemical drivers behind depression and suicidal tendencies associated with the disorder. Specifically, eating blueberries increase the expression of the gene SKA2 which is found to be decreased in those with those who are depressed and may show suicidal tendencies. The rat's blueberry diet was equivalent to about two cups per day for a person which, with the present price of blueberries, would be quite expensive.

Previously the researchers found that rats with the PTSD-like experience fed a blueberry-enriched diet showed increased levels of the signaling chemical serotonin in the brain. Psilocybin has a positive effect on the serotonergic system as well so there may be a good synergy here.

It was LSU researchers who were the first to isolate DMT (dimethyltryptamine) from the mammalian pineal gland which I have written about previously.

Of course eating 2 cups of blueberries a day will probably not cure anyone of PTSD but it does help to highlight the importance of diet, along with exercise and stress reduction towards mitigating the effects of PTSD.  But then again, if I ever have the opportunity to be part of a therapeutic session of psilocybin for PTSD, I'll be sure to follow it up with a big bowl of juicy, organic blueberries!

“There are moments when one feels free from one’s own identification with human limitations and inadequacies ... Life and death flow into one, and there is neither evolution nor destiny; only being.” — Albert Einstein

Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA

The article titled Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA was published in The Lancet Psychiatry on 5 April 2016. The article reviews the encouraging use of psilocybin and MDMA (I am personally opposed to the use of MDMA to treat PTSD as discussed below) for various psychiatric disorders and was written by Psychiatrists from UCLA and the University of South Carolina.

Below is the Summary from the 5 April 2016 article in The Lancet Psychiatry:

4-phosphorloxy-N,N-dimethyltryptamine (psilocybin) and methylenedioxymethamfetamine (MDMA), best known for their illegal use as psychedelic drugs, are showing promise as therapeutics in a resurgence of clinical research during the past 10 years. Psilocybin is being tested for alcoholism, smoking cessation, and in patients with advanced cancer with anxiety. MDMA is showing encouraging results as a treatment for refractory post-traumatic stress disorder, social anxiety in autistic adults, and anxiety associated with a life-threatening illness. Both drugs are studied as adjuncts or catalysts to psychotherapy, rather than as stand-alone drug treatments. This model of drug-assisted psychotherapy is a possible alternative to existing pharmacological and psychological treatments in psychiatry. Further research is needed to fully assess the potential of these compounds in the management of these common disorders that are difficult to treat with existing methods.

In a previous post, I mentioned that Jeffrey A. Lieberman, MD, currently chairman of psychiatry at the Columbia University College of Physicians and Surgeons and director of the New York State Psychiatric Institute and former president of the American Psychiatric Association, has endorsed research on psychedelic compounds in a Medscape post (free registration) stating they "need to be studied in an intensive and extensive way". Some passages from Dr. Lieberman's post for those without Medscape access:

• We have had a nearly 50-year hiatus in any serious investigation, except for some heroic investigators at a few universities, primarily in Europe but also in the United States.
• These psychedelic drugs clearly are pharmacologically active, have profound effects, could be useful for therapeutic purposes, and need to be studied in an intensive and extensive way before an informed determination can be made. 
• I believe that the scientific investigation of mind-altering psychedelic drugs in the 1960s and '70s was a truncated but promising avenue of research, and that these medications, these drugs, could have significant value for a variety of indications if studied adequately.

It is obvious that Psychiatry is showing increasing support for the use of psychedelics as therapeutic tools to treat various mental health issues.

The Lancet series of journals has a history dating back to 1823 with The Lancet being ranked second among general medical journals, (with an impact factor of 45), after The New England Journal of Medicine (impact factor of 56) according to the 2014 Journal Citation Reports. Johns Hopkins, which dates back to 1876, has been ranked among the top 10 in US News' Best National Universities Rankings and among the top 20 in a number of international rankings.

I mention both of theses highly regarded institutions due to the newly published Johns Hopkins-Lancet Commission on Public Health and International Drug Policy article and its call for non-violent minor drug offenses including use, possession, and petty sale, to be decriminalized internationally due to the serious detrimental effects on the health, wellbeing and human rights of drug users and the wider public. The article is titled 'Public health and international drug policy' and was published on 2 April 2016 in The Lancet. Authors of this study are from institutions to include Yale University, Columbia University, the UN, Johns Hopkins, UCSF, UCSD, and many prominent international Universities.

The article summary in MedicalXpress concludes:

• A number of countries, mostly in Europe, have decriminalized minor drug offenses with good results, including more ability to reach people with health and social services and better capacity of the police to focus their efforts on high-level trafficking offenses. Drug use, low-level possession and petty sale of drugs should not be subjected to criminal penalties, including prison sentences, and health and social services for drug users should be improved.
• People who use drugs have been shown in many countries to be keen to take advantage of prevention and treatment services, but they are often systematically excluded on the grounds of being thought unworthy or unreliable as patients. Governments should invest in comprehensive HIV, TB and hepatitis C services for people who use drugs. While sexually transmitted HIV is on the decline globally, HIV transmission linked to drug use is increasing. Comprehensive HIV, hepatitis C and TB services should be scaled up in prisons as well as in the community.
• Overdose deaths can be greatly reduced by ensuring that people who use opioids have good access to medication-assisted treatment and by ensuring that people who use drugs or are likely to witness overdoses have access to and are trained in delivering naloxone, a medicine that reverses overdose.
• Increasing numbers of national governments and sub-national jurisdictions (such as US states) are introducing legally regulated markets of cannabis. Governments and research bodies should see these as opportunities for rigorous scientific research and evaluation so best practices for public health and safety can be identified and emulated.
• Over-zealous drug control policies are limiting access to pain medications for legitimate clinical use in too many countries. Governments must find balanced policies for ensuring that people have access to controlled medicines such as opioids for the relief of pain while still impeding non-medical use of these substances.

While the focus of the Lancet article is on narcotics, this drug policy review details the futilities of the current approach to curtailing illicit drug use. Psilocybin is currently classified as a Schedule I drug by the DEA and the FDA based on the following criteria:

1. The drug or other substance has a high potential for abuse.
2. The drug or other substance has no currently accepted medical use in treatment in the United States.
3. There is a lack of accepted safety for use of the drug or other substance under medical supervision

As for the abuse potential, #1 on the list, notice the graph below which clearly shows psilocybin to be relatively free of dependency and toxicity issues.  Also notice how MDMA has a much higher dependency and toxicity potential than psilocybin.  So, let's scratch #1 off the list.  It just should not be there.

Data source is Gable, R. S. (2006). Acute toxicity of drugs versus regulatory status. In J. M. Fish (Ed.), Drugs and Society: U.S. Public Policy, pp.149-162, Lanham, MD: Rowman & Littlefield Publishers

Psilocybin, besides being less toxic than caffeine and lacking in dependency potential, has shown profound potential in treating addiction problems.  A small pilot study at Johns Hopkins enabled 12 of 15 (80%) subjects to remain tobacco free for 6 months.  Prescription medications such as Chantix, the most potent aid for smoking cessation, have a success rate of about 35% at six months. There are currently 2 other Clinical Trials utilizing psilocybin to treat addiction disorders: one for alcohol dependence and one for cocaine addiction.

As stated in the Lancet Psychiatry study that led off this post, psilocybin has shown encouraging potential for treating various mental health issues.  One of the most profound potentials of psilocybin is in treating the existential distress experienced by cancer patients or anyone with a life threatening diagnosis or having faced life threatening experiences (PTSD). So let's scratch #2 of the list as well.

As for #3, lack of accepted safety for use under medical supervision, all of the recent well-controlled, ethical Clinical Trials completed and ongoing have not shown any serious adverse effects.  So, lets take #3 off the list as well.  Where does that leave us now?

In my opinion, there should be a class-action lawsuit against the DEA and FDA forcing them to take hallucinogens off the Schedule 1 status to enable more ethical research to proceed for psilocybin.  

In an interview with John Ehrlichman, advisor to US President Richard Nixon, Ehrlichman explains that the War on Drugs was not to protect the American public but was ‘really about’ hurting ‘the antiwar Left, and black people’, and openly admits, ‘Did we know we were lying about the drugs? Of course we did’ (Baum, 2012).  We can now see how this policy was not to protect the American Public and in fact has hurt us. A recent (5-13-2016) article in Medical Daily titled 'The War on Drugs May Have Misrepresented Psychedelics; Here's Why That Matters' by Stephanie Kossman does an excellent job addressing this issue.

My objection above to the use of MDMA is first of a philosophical nature.  MDMA is synthetic. Psilocybin is natural and has a history of use for spiritual growth going back thousands of years. Second, MDMA displays an unacceptable degree of toxicity that psilocybin does not have.

My review of the research literature shows there are at least as many reasons not to use MDMA for PTSD as there are for its use.  By running a trial for PTSD using MDMA instead of psilocybin researchers are settling for use of an inferior compound with high levels of toxicity and dependence issues over psilocybin. I'm certain many researchers in the field share the same sentiments but are unwilling to speak up.

A case in point is the April 2016 publication of two articles, one involving psilocybin, the other MDMA.

In the article titled Meta-analysis of molecular imaging of serotonin transporters in ecstasy/polydrug users, researchers found that ecstasy users demonstrated significant reductions serotonin in the brain. which can impact appropriate emotional reactions to situations. They also noted that the effects on the serotonin system may underlie the cognitive deficits observed in ecstasy users.  MDMA is a drug that should be given a second look before using it in any Clinical Trials due to its neurotoxicity.

One the other hand, the April 2016 psilocybin study, Effects of serotonin 2A/1A receptor stimulation on social exclusion processing, has been given positive reviews by the media and demonstrates a keen applicability for treating PTSD.  It appears as though researchers have bet on the wrong horse so far in that there is are Clinical Trials using MDMA in the treatment of PTSD but none for psilocybin.

It is possible the MDMA researcher's goal leans more towards finding a use for MDMA than in finding the best treatment for PTSD which is unfortunate.

Prominent institutions such as Johns Hopkins have discussed using psilocybin in a Clinical Trial to treat PTSD but have yet to act on this idea.  In my opinion, the reason for this inaction is twofold. First, they realize MDMA is already involved in a Clinical Trial to treat PTSD and they do not want to step on those researcher's toes or to have two controversial trials treating PTSD.

The second reason is that, to my knowledge, none of the primary players in psilocybin research are military veterans.  I could be mistaken about this but have seen no mentions in the many CVs I've perused online to indicate such an association. If they had military experience, it would serve as an impetus to head in that direction. They should keep in mind that their right to perform their current research depends on the freedom we are currently enjoying in our society, a freedom many have died for.

If we are not careful, the current path of overpopulation and environmental destruction (Nature 6 April 2016) we are on could very soon put great stress on our way of life. Psilocybin may help us navigate our way out of this mess by contributing to a society with more openness and is less egocentric.

The American Chemical society now supports research into psilocybin and other hallucinogens

The American Chemical society has been around since 1876 and does not tend to support controversial topics.  On March 28, 2016, Chemical & Engineering News a weekly magazine published by the American Chemical Society, came out with a cover story titled 'Psychedelic compounds like ecstasy may be good for more than just a high'.

The article has separate essays on  ibogaine, MDMA, cannabis, ketamine, and psilocybin.  The psilocybin essay contains a quote from Dr. Roland Griffiths, a prominent researcher from Johns Hopkins stating:

“It was unlike anything I’ve seen in psychopharmacology before,” says Roland R. Griffiths, a professor of psychiatry and behavioral sciences at Johns Hopkins University, of his first trial examining the safety of psilocybin in healthy volunteers.

Those volunteers had positive effects that could last for years. “People had increased satisfaction and quality of life,” Griffiths says. “They felt more generous, centered, optimistic, and caring toward other people in their lives.” Patients’ friends, family members, and work colleagues confirmed the differences. 

We are moving in a positive direction.

Chronic pain, PTSD, mindfulness and psilocybin

Individuals with PTSD frequently experience chronic pain as well.  According to the Veterans Administration website on chronic pain and PTSD, approximately 15% to 35% of patients with chronic pain also have PTSD. Only 2% of people who do not have chronic pain have PTSD. One study found that 51% of patients with chronic low back pain had PTSD symptoms.

Just for the record, I am not a fan of the Veterans Administration when it comes to providing quality medical care for Veterans.  Although there are some notable exceptions, Veterans are provided with inferior medical care when compared with health care provided in the civilian sector. There is a culture at the VA where a significant percent of the employees have an attitude that the VA exists for them and having to deal with those Veterans is a pain in the ass. Plus they know it is almost impossible to get fired from the VA. I speak from experience having worked at 4 VA hospitals and having been a patient in 3 of them. It is time to shut it down and provide Veterans with the quality of care they deserve while saving taxpayers the expense of propping up a broken, outdated system.

Veterans should be allowed to receive local healthcare with a provider of their choice. What the Veterans Administration should focus on is research, in close collaboration with the Department of Defense, to improve medical treatment for issues that are unique to this population. I am not alone in criticism of the current care our Veterans are receiving. See New Commission on Care Report: VA Too Broken to Fix from the Federal Practitioner (6 April 2106).

Unfortunately many PTSD/chronic pain patients have been treated with opioids which are great for acute pain but very destructive for those with chronic pain.  Recent statistics provide an estimate of 40 deaths per day in the U.S. from the current epidemic of opioid prescription overdoses. In an attempt to address this issue the CDC has recently published new guidelines for prescribing opioids for chronic pain. CDC Director Tom Frieden, MD, MPH, stated in a news teleconference on 15 March 2016 just prior to the new guidelines. "For the vast majority of patients, the known, serious and all too often fatal risks far outweigh the unproven and transient benefits, and there are safer alternatives."

So what are some of the safer alternatives and why do individuals with PTSD tend to experience more chronic pain than those without PTSD?  This essay will attempt to clarify these issues.

On 22 March 2016, the Journal of the American Medical Association (JAMA) published a very timely article regarding research that attempts to find a nonpharmacologic approach to treating low back pain (LBP).  The article is titled "Effect of Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy or Usual Care on Back Pain and Functional Limitations in Adults With Chronic Low Back Pain: A Randomized Clinical Trial" and is freely available online.

Results of this breakthrough study concluded "among adults with chronic low back pain, treatment with mindfulness-based stress reduction (MBSR) or cognitive behavioral therapy (CBT), compared with usual care, resulted in greater improvement in back pain and functional limitations at 26 weeks, with no significant differences in outcomes between MBSR and CBT. These findings suggest that MBSR may be an effective treatment option for patients with chronic low back pain."

It should be noted that while the researcher in this study were primarily from the University of Washington, Seattle, the mindfulness-based stress reduction (MBSR) program they utilized was developed at the University of Massachusetts Medical Center in the 1970s led by Jon Kabat-Zinn.  Becoming trained as a provider in MBSR involves much more than getting a certificate for having taken a weekend course.  To be effective, you must be a practitioner of MBSR yourself which takes much dedication and training. Therefor finding  therapist trained in MBSR can be rather difficult but still much easier than finding a therapist trained to lead you through a therapeutic psilocybin session.

Just 5 days prior to the release of the JAMA study, the National Institutes of Health (NIH) commented on a newly released study published in the Journal of Neuroscience titled "Mindfulness-meditation-based pain relief is not mediated by endogenous opioids" that was partially funded by the NIH. The authors of the study concluded "results demonstrate that meditation-based pain relief does not require endogenous opioids. Therefore, the treatment of chronic pain may be more effective with meditation due to a lack of cross-tolerance with opiate-based medications." This study is important because opioid and non-opioid mechanisms of pain relief can interact synergistically to increase the effectiveness of pain control.

Although the Journal of Neuroscience study does not indicate what the non-opioid pathway may be, there is a plethora of evidence to suggest that it may involve the default mode network (DMN).  Hyperconnectivity of the default network has been linked to rumination in depression and chronic pain. Mindfulness meditation and therapeutic use of psilocybin both have shown similar functions in reducing activity of the DMN.

A key structure within the default mode network is the posterior cingulate cortex which is activated during self-referential thinking and deactivated during meditation and psilocybin intake. It is possible that decreasing self-referential processing distracts the individual from ruminating over their life condition and allows them to have the experience of being connected to the world outside themselves and to live a more contented, productive life with a significant decrease in pain. Individuals who have taken psilocybin as part of a Clinical Trial for cancer patients have made statements indicating that after taking psilocybin they just do not pay that much attention to their pain anymore.

After all these years, it is very satisfying to have the CDC, NIH, and JAMA all joining me in an attempt to treat conditions like chronic pain and PTSD in a nonpharmacologic manner such as mindfulness.  If medication is needed, lets stick with the natural non-addictive variety such as psilocybin. Besides being non-addicting, psilocybin has shown profound medical benefits and need only be taken a once or twice - a pharmaceutical company's nightmare.

Psilocybin use implicated in a reduction of intimate partner violence

The recent study by Peter S. Hendricks, Ph.D., University of Alabama Birmingham (UAB), Department of Health Behavior, had been placed on the University of Alabama News website a few weeks ago but is now no longer available.  The reason for this in not known.  Also, the journal this research will be published in is also not yet known.

Still, the information that was once on the website has been preserved by other websites such as MedicalXpress.  MedicalXpress (a great source of the most recent medical news) gives UAB as the source of its information.  Here is a link to the article from MedicalXpress titled Hallucinogens use could protect against intimate partner violence.

The study 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. Hendricks 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."

I'll keep you posted regarding the publication of this study and hopefully an explanation as to why the information was removed from the UAB website.

From Dr. Hendricks' CV, it is noted that he has shown a lifetime dedication to assisting those with substance abuse issues.  I sincerely hope his recent interest in the use of psychedelics towards this end will not have a negative impact on his career.  This has happened in the past but hopefully the current renaissance in psychedelic research will be allowed to continue as long as the researchers follow their current rigorous scientific standards and ethical behavior.  The science is there to support this research and there is no room in science or medicine for bias.

Twenty years ago, Dr. Henricks most likely would have been fired for promoting research on psychedelics. Now there are groups sprouting up all over the world encouraging like-minded individuals to share their support and experience with these sacred, entheogenic substances (synthetics such as MDMA not included).  A search for entheogens in Meetups highlight this global support.

Update (04/25/2016): Dr. Hendricks article has now been published in the Journal of Psychopharmacology and is titled Hallucinogen use and intimate partner violence: Prospective evidence consistent with protective effects among men with histories of problematic substance use

A recent article in Aggression and Violent Behavior (March/April 2016) by researchers from The University of Western Ontario titled Recreational drug use and human aggressive behavior: A comprehensive review since 2003  backs up Dr. Hendrick's research with the following conclusions:

• Alcohol causes aggression.
• Cannabis is correlated with aggression, and personality mediates this association.
• The research on methamphetamines, opiates, and stimulants and aggression is complex.
• Hallucinogens such as psilocybin reduce aggressive behavior.
• Psilocybin is associated with positive spiritual and mystical experiences.
• Psilocybin significantly alleviates symptoms of obsessive–compulsive disorder.
• Low doses of psilocybin extinguished the conditioned fear response to an adverse stimulus in an animal model of PTSD.
• Psilocybin positively impacts hippocampal neurogenesis.
• Psilocybin was proposed as a potential treatment for Posttraumatic Stress Disorder.

PTSD is associated with an increase in intimate partner violence. A large epidemiological study of Vietnam and Vietnam-era Veterans that was conducted in the mid-1980s examined intimate partner violence (ranging from slapping and pushing to using a knife or gun), and found that 33.0% of Veterans with PTSD compared to 13.5% of those without PTSD reported intimate partner violence in the past year (1). Considering all of the many positive properties of the therapeutic use of psilocybin, a reduction in intimate partner violence is another benefit to add to the list.  PTSD is not seen just in the military and in Veterans. Soon, due to the coming global climate catastrophe, the majority of the earths population will have PTSD so we best start investigating psilocybin as a treatment ASAP.

For some health care providers, the lack of effective treatments for conditions such as PTSD, addictions, suicidal thoughts, depression, and fear of death leads them, out of compassion and empathy, to assist those suffering by guiding them through psychedelic therapy in violation of the law.  To me, these brave souls are true 'Heroes of the Universe'.  They are heroes as they are giving their live's for a cause great than themselves.  The goals is to provide those suffering with a sense of unity, a shared universal consciousness, which reveals all of our interconnectedness.

I sincerely hope the laws change soon so these compassionate beings do not have to suffer the consequences of unfair and misguided laws.  Psychedelics should be removed from Schedule I classification as they are neither addicting nor lacking in medical benefit.  A recent article in The Atlantic questions whether current psychedelic drug laws violate our basic human rights?

1. Jordan, K. B., Marmar, C. R., Fairbank, J. A., Schlenger, W. E., Kulka, R. A., Hough, R. L., & Weiss,       D. S. (1992). Problems in families of male Vietnam Veterans with posttraumatic stress disorder. Journal       of Consulting and Clinical Psychology, 60, 916-926. doi: 10.1037//0022-006X.60.6.916 (PDF)

Comment on use of transcutaneous trigeminal nerve stimulation for PTSD

Exploring non-pharmacologic means to treat PTSD will always  get a thumbs up from me.  The results of a recent Clinical Trial exploring the use of transcutaneous trigeminal nerve stimulation was just published in the journal Neuromodulation: Technology at the Neural Interface. Study results were modest but what is most intriguing is how stimulating the trigeminal nerve would have a positive effect on PTSD and also, from previous studies, positive effects on reducing the frequency of epileptic seizures.

Monarch™ eTNS™

Looking at the Neurosigma website, the company who's product the Monarch™ eTNS™ is behind this research, they point out that the trigeminal nerve is the largest cranial nerve.  Yes it is considered by some
criteria to be "the largest" but the vagus nerve is the longest cranial nerve and by far the most complex.  The vagus nerve supplies vital organs, is the primary parasympathetic nerve, plays a vital role in our immune system, and helps to control systemic inflammation.

Also, they do not call the superficial stimulation of the trigeminal nerve with the Monarch transcutaneous stimulation but refer to it as external stimulation.  I'm wondering if that is for marketing purposes.  Why purchase a Monarch if a similar function can be served by a transcutaneous nerve stimulator?

As to how the trigeminal nerve, a nerve whose primary function is for sensory and motor functions in the face and mouth regions, can have such systemic effects on complex disorders such as PTSD and epilepsy, the answer may come from tracing the path of the trigeminal nerve. The nucleus tractus solitarius, located in the dorsomedial medulla, does receive a few projections from the trigeminal nerve.  The Neurosigma website points this out.  They also state the involvement of the locus coeruleus in the proposed mechanism for the effects of trigeminal nerve stimulation. Again, there are some connections. The vagus nerve supplies dense connections to the these structures, not just a few fibers.

Regarding the proposed involvement of the locus coeruleus in the etiology of trigeminal nerve stimulation, therapy, recent research has shown that the antidepressant effects of vagus nerve stimulation (VNS) is via the locus coeruleus (LC).  Here are some highlights of that study (Journal of Psychiatric Research Sep 2015):

• VNS has an antidepressant-like effect in the forced swim test.
• Lesioning the LC abolishes this antidepressant-like effect of VNS.
• Our results support a key role for the LC in the antidepressant mechanism of VNS.
• The results of this study demonstrate that the noradrenergic neurons from the LC play an important role in the antidepressant-like effect of VNS. 

Just last week (Feb 16, 2016) a new study has added a key piece to the Alzheimer's puzzle by demonstrating the locus coeruleus to be 'ground zero' in the etiology of Alzheimer's:

Researchers highlight brain region as 'ground zero' of Alzheimer's disease
The locus coeruleus is a small, bluish part of the brainstem that releases norepinephrine, the neurotransmitter responsible for regulating heart rate, attention, memory, and cognition. Its cells, or neurons, send branch-like axons throughout much of the brain and help regulate blood vessel activity. Its high interconnectedness may make it more susceptible to the effects of toxins and infections compared to other brain regions, said lead author Mara Mather.

Mather, Professor of Gerontology and Psychology at the University of Southern California Leonard Davis School of Gerontology, added that the locus coeruleus is the first brain region to show tau pathology—the slow-spreading tangles of protein that can later become telltale signs of Alzheimer's disease. Though not everyone will get Alzheimer's, autopsy results indicate that most people have some initial indications of tau pathology in the locus coeruleus by early adulthood, she added. Trends in Cognitive Sciences March 2016

It appears to me to be quite clear that transcutaneous vagus nerve stimulation (see previous post) could play a key role in protection from Alzheimer's disease and there is a new Clinical Trial starting very soon to test that hypothesis. Details from the Clinical Trial:
There are three aims in this project:

1. To investigate how the functional interaction between the locus coeruleus and other brain areas, in particular the medial temporal lobe areas, during memory processes (encoding, consolidation and retrieval) change with development of Alzheimer's disease.
2. To investigate associations between noradrenaline, memory performance and brain functioning. The investigators aim to investigate how acute noradrenalin levels change during the different memory processes and whether or not this is beneficial for performance. Furthermore, the investigators will investigate whether this interaction between noradrenalin, memory performance and brain functioning is different healthy older individuals (n =35) or patients with prodromal Alzheimer's disease (n =35).
3. To investigate the underlying neural network changes during transcutaneous vagus nerve stimulation. The investigators will focus on differences in functional connectivity between the locus coeruleus and the medial temporal lobe areas in healthy older individuals and prodromal Alzheimer's disease patients. An experimental condition will be compared with a sham condition in a pseudo-randomized cross-over design.

After some initial excitement regarding the potential of trigeminal nerve stimulation, it appears as though stimulating the trigeminal nerve is just acting as a middleman to achieve the same or better effects that can be achieved using vagus nerve stimulation.  Neurosigma does state "The NTS is a key regulator of the parasympathetic, or “rest and digest” nervous system, and provides a direct connection between the trigeminal and vagus nerve systems." So lets just cut out the BS and go for the gold.

This is not a technology I would invest in.  Best bet, in my opinion, cut out the middleman and go right to the source - stimulate the vagus nerve to treat PTSD.  DARPA, the Defense Advanced Research Project Agency has been funding research on vagus nerve stimulation to treat PTSD. DARPA's research appears to focus on the vagus nerve with no mention of the trigeminal nerve. As for a potential new Clinical Trial, perhaps stimulating the auricular branch of the vagus nerve and the trigeminal nerve simultaneously would provide some sort of synergist effect as opposed to just stimulating the vagus nerve.

Bindi and Third Eye

Another possible explanation for the positive effects of transcutaneous trigeminal nerve stimulation is it's effect on the "third eye" as the locations on the forehead are the same..  The "third eye" is a mystical concept that turns out to have real evolutionary significance. There are some 'primitive' extant reptiles such as the Tuatara which has a parietal eye that in 'higher' vertebrates became the pineal gland. The FDA approved Cefaly for migraines appears to be capitalizing on this concept by its design. Dimethyltryptamine (DMT) has been shown to be produced by the mammalian pineal gland. Interesting!

The Cefaly trigeminal nerve stimulator for migraines - Third Eye?

Transcendental Meditation for treating PTSD

A new article in Military Medicine (Jan 2016) details research performed by military medical personnel at Dwight David Eisenhower Army Medical Center's Traumatic Brain Injury Clinic at Fort Gordon, Georgia. 74 active-duty service members with PTSD or anxiety disorder were divided into experimental and control groups with both receiving treatment as usual and the experimental group also receiving training in and practice of Transcendental Meditation (TM).  The experimental group receiving the extra TM training and practice were able to "reduce or even eliminate their psychotropic medication and get better control of their often-debilitating symptoms."

While I applaud their approach and the willingness of military personnel to undertake such timely research, I do have a few issues with their work.  First, it appears the control group did not receive an equal amount of extra staff attention and were not assigned a task that would also take an equal amount of time daily to do something akin to just sitting quietly for 20 minutes twice a day.  This was not a properly controlled study and does little to show anything special about TM.

Not that there isn't anything special about TM, it is just that this study design fails to show it. What David Lynch is doing with the Operation Warrior Wellness (OWW) program is highly commendable. Maharishi Mahesh Yogi's efforts to spread the practice of meditation globally should have won him the Nobel Peace Prize and his book Maharishi Mahesh Yogi on the Bhagavad-Gita : A New Translation and Commentary, Chapters 1-6 was a classic.  It is unfortunate he did not have time to translate the last 12 chapters. According to TM, the key is to 'be without the three gunas'. Being without the three gunas is, in essence, a state of non-judgemental mindfulness.

Still, I'm not convinced that TM has any special edge over other meditation techniques.  This is not a competition.  Comparing gurus is one step in the direction of cutting off someone's head because they do not believe what you believe. Just getting more people to meditate and quiet their sympathetic nervous system and default mode network would be a major step forward towards saving humanity from our possible path of self-destruction.

EMWave2

If these researchers want to be on the cutting edge of research in this field, there are at least two additional steps they can take. First they can supplement the effectiveness of participants meditation progress using heart rate variability biofeedback (HRV-b).  Having instant feedback on how you are progressing is extremely valuable. Increasing heart rate variability through biofeedback has been shown to improve the balance between the parasympathetic and sympathetic nervous system. There is a relatively inexpensive unit, the EMWave2 available from HeartMath that has been utilized in many studies to include some by the military.

My personal experience with the EMwave2 has been positive.  It's cost is not prohibitive ($200 dollars) although its durability can be improved.  My units tend to peter-out after about 1 year of fairly constant use. The best aspect of this form of non-intrusive biofeedback is its ability to keep you in a state of mindfulness.  When I find my mind wandering, the EMWave2 informs me which makes it a great adjunct to meditation.

I'm not sure if the EMWave2 uses a linear or non-linear algorithm to monitor heart rate variability (they will not divulge this information). The output it provides lets you know when the parasympathetic and sympathetic nervous systems are in balance and is referred to as coherence.

Vagus nerve in green

Electrical stimulation of the auricular branch of the vagus nerve has been shown to decrease sympathetic nerve activity, to increase vagal tone, and to activate the cholinergic anti-inflammatory pathway. The ear is the only place the vagus nerve is superficial and able to be stimulated non-invasively. The increase in vagal tone is achieved without the use of medication and is non-invasive. Decreasing systemic inflammation via the cholinergic anti-inflammatory pathway and increasing vagal tone have shown positive results for treating depression, chronic pain, PTSD, cancer, atrial fibrillation, stroke, heart failure, rheumatoid arthritis to mention a few. The cholinergic anti-inflammatory pathway is a recently described, vital part of the immune system who's role in various disease states is only recently being ascertained.

Vagus nerve stimulation
 with
TENS electrodes

Electrical stimulation of the auricular branch of the vagus nerve has great potential to play a key role in treating many diseases of modern society, it can modulate the default mode network, and that it can be manipulated without drugs is a big plus. What is so amazing is very few physicians have an interest in this process even though it involves a key part of our immune system.  I guess when some drug company comes out with a drug they can write a prescription for then they will start showing some interest.

DARPA, the Defense Advanced Research Project Agency, inventors of the internet (sorry Al Gore) and the premier agency for United States military research, has been funding research on vagus nerve stimulation to treat PTSD. From their website Work Begins to Support Self-Healing of Body and Mind:

"A team at the University of Texas, Dallas, led by Robert Rennaker and Michael Kilgard, will examine the use of vagal nerve stimulation to induce neural plasticity for the treatment of post-traumatic stress. As envisioned, stimulation could enhance learned behavioral responses that reduce fear and anxiety when presented with traumatic cues. Dr. Rennaker is a U.S. Marine Corps veteran who served in Liberia, Kuwait and Yugoslavia."

Not a recommendation but this product found on Amazon may serve the purpose of stimulating the auricular branch of the vagus nerve.

New article from Biological Psychiatry (Feb 2016) from Harvard, Medical College of Wisconsin, and China titled Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder involves stimulation of the auricular branch of the vagus nerve to treat depression and demonstrates its effect on the default mode network.

There is new research involving activation of the locus coeruleus via transcutaneous vagus nerve stimulation and it role in prevention of Alzheimer's.  See details in the next post.

Quiet the Default Mode Network and save the world

It has been demonstrated with fMRI that mindfulness meditation and psilocybin (a must read) both decrease activity in the default mode network and both can promote the experience of oneness, a sense of timelessness, a profound sense of sacredness, and can result in an overall decrease in anxiety. These are qualities that are lacking in the present efforts to deal effectively with global issues of terrorism, climate change, and extreme political polarization.

A new article in the journal Cerebral Cortex used fMRIs to measure brain activities in 3 different cultural groups (Chinese, American and Iranian) while they were reacting to narratives that involved core, protected beliefs. Researchers found increased activity in the “default mode network” when these core, protected values were contemplated.

A press release from the University of Southern California details key aspects of the study.  The press release concludes:

It’s not yet clear whether a value either is or is not protected, or whether the sacredness of a value is on a sliding scale. But in a nation where political beliefs are growing more polarized and entrenched, it’s important to understand what biological processes lie at the root of these values, Kaplan said.

“People will often hold political values as protected values and protected values are at the root of many political conflicts around the world, which is why they’re interesting to us,” he said.

Just a reminder, taking psilocybin is not a game.  It must be done for the right reasons and with proper supervision.  Set and Setting are key.

This one has a very chaotic, out of control default mode network and would not be good for world peace.  He also can not spell and has difficulty with complex issues which limits him to derogatory, grade school level one liners. These characteristics remind me of a former President except this one is not as genial.  Early Alzheimer's?

This gentleman has a very quiet default mode network which is reflected in his face, in his eyes.  He does not take himself too seriously and his ego is not an obstacle to world peace.  Yoda's eyes were patterned after Einstein's eyes.

Psilocybin: a single dose relieves Existential Distress in cancer patients

Location: 2015 Meeting of the American College of Neuropsychopharmacology
Date: 10 December 2015
Synopsis: Dr. Roland Griffiths (Johns Hopkins) presented some pre-publication results of a study that utilized psilocybin to reduce the anxiety and depression that frequently accompanies patients with a life threatening cancer diagnosis. Patients receiving relatively high doses of psilocybin sufficient to induce changes in perception and to frequent a mystical experience reported significantly decreased levels of anxiety and depression compared with patients that received a low dose of the drug. The positive effects on mood were still present in those patients at a 6 month follow-up. Both Johns Hopkins and NYU have recently completed studies with cancer patients given therapeutic doses of psilocybin although there were nuances that made each study unique.  My best guess is their research may be published in early 2016.  It is my hope they will both be published at the same time, separately but in the same journal/issue for maximum public/media impact.

The following is from the meeting abstract found in Neuropsychopharmacology (2015) 40, S1–S105:

Methods: The study used a randomized, double-blind, cross-over design to investigate the acute and sustained effects of a very low psilocybin dose (1 or 3 mg/70 kg) vs. a moderate-high dose (22 or 30 mg/70 kg). Instructions to participants and staff minimized expectancy effects. 51 patients with a life-threatening cancer diagnosis who had symptoms of anxiety or depression received a low or high dose of psilocybin in counterbalanced order with about 5 weeks between sessions and a final follow up at 6 months. For this preliminary analysis, results between the low (n=25) and high (n=26) dose groups on the first session were compared. Enduring effects were assessed at a 6 month follow-up.
Results: On session days, the high dose group showed substantially greater effects including perceptual changes, mystical-type subjective experiences, and labile mood. At the 5-week follow-up the high dose group showed significantly lower anxiety (STAI Trait Anxiety, HAM-A) and depression (BDI, HAM-D) compared to the low dose group (effect size mean and range 0.98, 0.60-1.30). The participants attributed significantly greater positive changes in attitudes about life/self, positive social effects, and positive behavior changes to the experience, and a higher percentage reported the experience to be among the 5 most personally meaningful of their lives (54% vs. 16%). Total mystical experience scores at the end of the session showed significant negative correlations with the above measures of anxiety and depression at 5 weeks. Partial correlation analysis showed this relationship remained significant after controlling for ratings of intensity of drug effect. The decreases in anxiety and depression were sustained at 6 month follow-up.
Conclusions: A single moderate-high dose of psilocybin, when administered under supportive conditions to carefully screened and prepared participants, can produce substantial and enduring decreases in anxiety and depression in patients with a life-threatening cancer diagnosis.

My assessment: Psilocybin is non-addicting with less toxicity than caffeine. There are no currently available medications that improve cancer patient's mental health this significantly and it only has to be taken once or twice with the proper Set and Setting. Cancer patients with a life threatening diagnosis often experience a profound Existential Distress as do those with PTSD so it is reasonable to expect psilocybin given in a therapeutic dose in a supportive environment will provide a similar benefit to those with PTSD.

DoD and/or VA researchers, the science is there, it just needs to be followed.  Those with PTSD need your help and courage.

A New Understanding: The Science of Psilocybin in an excellent 1 hour documentary that profiles two cancer patients, both now deceased, who had experienced profound benefit from participating in the psilocybin trials being conducted at Johns Hopkins, UCLA and NYU. A panel discussion following the screening of the documentary 'A New Understanding: The Science of Psilocybin' is 1.5 hours long and features many of the researchers producing this life altering knowledge. During the panel discussion, it was mentioned that an application for compassionate use was submitted to the FDA for cancer patient to be allowed access to psilocybin but they were doubtful it would be passed.

“Man is not destroyed by suffering. He is destroyed by suffering without meaning.” Victor Frankl

Microdosing psilocybin

The focus of this website is to encourage psilocybin research for the treatment of PTSD. However, there has been numerous news articles recently exploring the use of microdoses of psilocybin and other 5-HT2A receptor agonists.  Reported benefits include lifting of depression, increased energy, and increased creativity. Two of these articles have been from prominent, traditional publications:

• Short Trip? More People 'Microdosing' on Psychedelic Drugs  NBC News July 2015
• LSD Microdosing Deserves More Serious Research  Forbes November 2015

James Fadiman Ph.D., who has been involved with psychedelic research since the 1960's, published a book in 2011 titled The Psychedelic Explorer's Guide: Safe, Therapeutic, and Sacred Journeys.  One chapter of the book is devoted to microdosing.

I'm not sure at what point a "low dose" becomes a "microdose" but the concepts are similar.  In an earlier post, "Comment on low dose psilocybin for treatment of PTSD", I discussed how The article by Catlow BJ et al. (Exp Brain Res. 2013 Jun 2. [Epub ahead of print]), demonstrates how a low dose (0.1 mg/kg) of psilocybin helps mice overcome a conditioned fear response significantly quicker than a medium (0.5 mg/kg) or high dose of psilocybin (1.0 mg/kg) and results in hippocampal neurogenesis while the higher doses result in a decrease in cell survival.

Antidepressant medication known as SSRIs (serotonin reuptake reuptake inhibitors) are thought to work by increasing synaptogenesis/neurogenesis.  Given the results of the Catlow study above, it is reasonable to conclude that microdosing also results in an increase in hippocampal synaptogenesis/neurogenesis as well.

The good thing about microdosing with psilocybin is that no prescription is required.  The bad thing about microdosing with psilocybin is that no prescription is available. This discrepancy will change when Federal authorities move psychedelics from Schedule I to Schedule II status. Reclassification as schedule II will allow unimpeded research to determine how it works, effective dosages, and potential side effects.  Since a significant portion of the American public is attempting to work this out themselves, professional guidance would be prudent.

A recent article in the Journal of the American Medical Association (Aug 4, 2015) found that current treatments for post-traumatic stress disorder (PTSD) such as Prolonged Exposure Therapy and Cognitive Processing Therapy are not proving effective. "There is a need for improvement in existing PTSD treatments and for development and testing of novel evidence-based treatments, both trauma-focused and non–trauma-focused".   Psilocybin is a novel treatment that deserves to be investigated as it holds great promise to end the suffering of many with PTSD when provided with appropriate Set and Setting. The therapeutic psilocybin sessions could be couched within concurrent Cognitive Behavioral Therapy to allow the therapeutic integration of the psychedelic/spiritual experience. The JAMA article above has been cited by (Google Scholar).

NSI-189

Another promising antidepressant, NSI-189, has just completed a phase 1B Clinical Trial, led by Massachusetts General Hospital (MGH) investigators with the results published in Molecular Psychiatry on 8 December 2015 (PDF). What makes this compound especially promising is it a nicotinamide derivative that was first developed as part of a Defense Advanced Research Projects Agency (DARPA) funded program and it promotes hippocampal neurogenesis. Niacin, or vitamin B3, is rapidly converted into nicotinamide after ingestion.

Astaxanthin and exercise are two additional adjuncts to hippocampal neurogenesis.

Choosing compounds that are closely related to natural, essential nutrients and avoiding halogenated hydrocarbons may be a wise choice.  Many pharmaceutical companies will add a fluorine or chlorine atom to an organic compound to give it a specific shape.  The addition of a halogen to an organic compound will frequently increase it's toxicity. "Unlike the aromatic or aliphatic hydrocarbons, the halogenated hydrocarbons tend to cause a wider range of toxicity" (source Medscape). A good method of determining if drugs have added halogens is to look in Wikipedia for the chemical structure of to Google the drug name with the added term 'structure' in the search.  Next choose 'Images' as the Google option.  Examples:

NSI-189 (Wikipedia)

NSI-189 (Google Images)

If you own a pet and treat them for fleas, you may want to stay away from Frontline for fleas. This is the 'Mother of all halogenated hydrocarbons' and I'm wondering if it doesn't increase cancer rates significantly.

Veterans Administration researcher promotes psilocybin research

Richard Andrew Sewell M.D with the Department of Psychiatry, West Haven Veterans Affairs Hospital, West Haven, CT and others have just published an article in the Journal of Psychoactive Drugs titled:

Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey
Cluster headache is one of the most debilitating pain syndromes. A significant number of patients are refractory to conventional therapies. The Clusterbusters.org medication use survey sought to characterize the effects of both conventional and alternative medications used in cluster headache. Participants were recruited from cluster headache websites and headache clinics. The final analysis included responses from 496 participants. The survey was modeled after previously published surveys and was available online. Most responses were chosen from a list, though others were free-texted. Conventional abortive and preventative medications were identified and their efficacies agreed with those previously published. The indoleamine hallucinogens, psilocybin, lysergic acid diethylamide, and lysergic acid amide, were comparable to or more efficacious than most conventional medications. These agents were also perceived to shorten/abort a cluster period and bring chronic cluster headache into remission more so than conventional medications. Furthermore, infrequent and non-hallucinogenic doses were reported to be efficacious. Findings provide additional evidence that several indoleamine hallucinogens are rated as effective in treating cluster headache. These data reinforce the need for further investigation of the effects of these and related compounds in cluster headache under experimentally controlled settings.
Schindler EA, Gottschalk CH, Weil MJ, Shapiro RE, Wright DA, Sewell RA.
J Psychoactive Drugs. 2015 Nov 23:1-10. [Epub ahead of print]
PMID: 26595349

Just as psilocybin can be "comparable to or more efficacious than most conventional medications" for cluster headaches, psilocybin may be the best medication available for PTSD.  Researchers will not know this if they do not run any Clinical Trials utilizing psilocybin to treat PTSD.

Unfortunately the study was published posthumously for Dr. Sewell who died in 2013 following surgery at Yale-New Haven Hospital. Hats off to this heroic researcher and condolences to his friends and family.