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.