June 04, 2018

Introduction to the problem and how we got it so wrong:

 

 While the science of opioid use, addiction and treatment of addiction is very scientific and complex, this essay seeks to tell a straight forward simple story for all. We do leave, for those wishing to study this topic more deeply, some reading materials and resources below.

 

All of the observations and conclusions in this essay come from respected peer reviewed literature and reports. For instance, the observation that CBD is reported as safe and non-addictive is lifted from a recent report by the World Health Organization.

 

The derivatives of Cannabis sativa are classified as Schedule 1 Drugs, right alongside heroin and cocaine. To be classified as a Schedule 1 Drug it is required that there is absolutely no value or benefits to its use.  No less than Dr. Sanjay Gupta has come to such a strong conclusion about the value of CBD in treating opioid addiction that he sent a very detailed and strong letter recently to Attorney General Sessions asking that this classification be changed.  

 

This is not the first time our government has gotten things very badly wrong in terms of health and diet and drugs. For instance, we were advised for decades to avoid eggs, natural butter, sugar, and encouraged to use margarine, hydrogenated oils, load up our caloric intake by avoiding meat and fish and fat, and go for an abundance of starches, things like bread and pasta and potatoes etc. So, this brought us nationally to an extreme state of obesity and an epidemic of Type II Diabetes and heart disease.

 

One of my colleagues thought there might be conspiracy and collusions behind all this that the government got so badly wrong over and over again over five decades. I think not. This is what I think:

 

  1. Many of the leaders of industry are just crooks, corrupt to their souls. For instance, the leaders of these very large industrial companies and industrial complexes are led by very smart and very diligent and aware people:

 

  1. I cannot imagine being convinced that for many decades the tobacco executives did not know in their minds and souls how bad smoking was for health;
  2. Same for the sugar and artificial sweetener firms;
  1. Same for the makers of hydrogenated oils and fats;
  2. And soft and sugared and sweetened drinks.

 

  1. I don’t think there is much venal corruption in our government. But malfeasance, incompetence and being overwhelmed by industry and being assailed by short-sighted mildly corrupt fund raising politicians? Surely this is how these things happened.

 

So, on one side we have moral and ethical and even criminal corruption in industry. And on the other we have malfeasance, incompetence, and being overwhelmed, while being assailed by “paid experts” and politicians in self-serving fund-raising actions applying pressure for their constituents, the industry. One hand washes the other between politicians and industry.

 

The FDA and industry approved oxycodone based on the idea it is a great pain killer and less addictive. This is patently wrong and dishonest and insane. If they did not actually know it on day one, two years later the proof coming in was overwhelming.

 

We are 15 years into this self-inflicted epidemic.  For a stunning insight: It is widely recognized by the drug cartels that an enormous market was created for them into which they could sell illicit opiates. It was and is being created for them by medically over prescribed exogenous opioid painkilling drugs: this did the job of creating a gateway bringing clients to them. No longer did they have to come up with strategies to get children and young peopled addicted: the MDs were writing prescriptions to the full demographic cross section of America, bringing new clients to the drug cartels in numbers far beyond anything they ever dreamed to serve.

 

It took no time for folk to become addicted, and as they needed more opioids to sustain the effect, to figure out that crushing the pills bypassed the time release mechanism. When the prescriptions dry up, heroin is one of the best ways to avoid withdrawal. The entire affair of oxycodone and the like is likely to end up as a criminal affair and be right up there with the Tobacco industry’s fraud and misrepresentation of the effects of tobacco.

 

Marijuana has been called the “Gateway Drug”. In this case our government got it half right. CBD is a gateway agent. It is not a drug. It is safe, it is not addictive, no illness or fatality or emergency room visit has been recorded globally for a CBD overdose. It is a gateway, it is a natural nutraceutical agent, it is the gateway for an exit from addiction, a gateway out of hell.

 

Background:

 

 We all have an opioid system active in our biology, it is one of many systems, many of which interact.  Our opioid system operates normally and naturally in all of us based on endogenous opioids, ones we make and process in our normal biological operations. These are healthy and good.

 

But there are also the exogeneous opioids, the drugs and pain killers. These for the most part, perhaps all of them, are neurotoxins. They exercise an enormous impact on our opioid and other systems in ways that create euphoria, mitigate pain but also at the same time rewire our brains. One needs to take increasingly larger doses to sustain an effect, making us increasingly and seemingly permanently dependent. This rewiring causes withdrawal upon cessation of using of the exogeneous opioids, the onset of hyper sensitivity, which is called withdrawal. Until we correct this rewiring, the addiction is not cured.

 

Thomas R. Kosten, M.D. and Tony P. George, M.D. in their article The Neurobiology of Opioid Dependence: Implications for Treatment describe this thus:

 

“Brain abnormalities resulting from chronic use of heroin, oxycodone, and other morphine-derived drugs are underlying causes of opioid dependence (the need to keep taking drugs to avoid a withdrawal syndrome) and addiction (intense drug craving and compulsive use). The abnormalities that produce dependence, well understood by science, appear to resolve after detoxification, within days or weeks after opioid use stops. The abnormalities that produce addiction, however, are more wide-ranging, complex, and long-lasting. They may involve an interaction of environmental effects—for example, stress, the social context of initial opiate use, and psychological conditioning—and a genetic predisposition in the form of brain pathways that were abnormal even before the first dose of opioid was taken. Such abnormalities can produce craving that leads to relapse months or years after the individual is no longer opioid dependent.”

 

This story is a simple summation of a much more complex context. Here is the summary of the observations from the literature that will form the foundation of my conclusions:

 

  1. Exogeneous opiates (heroin, oxycodone, and most all morphine derived drugs) rewire the brain leading to craving for increased doses, diminution of effect of a dose over time, and extreme hypersensitivity upon cessation of taking these drugs, characterized as withdrawal.

 

  1. CBD is the highest concentrated cannabinoid in Industrial hemp, and second highest in Cannabis sativa, marijuana, after THC. CBD has no psychoactive effects. CBD is not addictive, it is safe, it relieves pain, and has been identified as a neurogenesis agent, not a neurotoxin. It not only relieves the pain and mitigates the hypersensitivity of withdrawal from exogenous opiates, over time it heals the damage to the brain caused by the exogenous opioids, the rewiring caused by the use of neurotoxic exogenous opiates.

 

  1. CBD has a very weak even negligible interaction with both the CB1 or CB2 receptors in the endocannabinoid system, which is why it is not psychoactive. These receptors require a molecule with a planer morphology. Though CBD and THC, the later being the psychoactive agent of the cannabinoids, and CBD being the non-psychoactive member, have the same molecular formula and weight, THC is planer. But there is a 90 degree angle between the rings in CBD. This makes the earlier reactive with the CB1 and CB2 receptors and makes CBD unable to react with these CB1 and CB2 receptors.

 

  1. CBD is recognized as being involved in neurogenesis. It is not a toxin, it is an agent of healing. More about this below.

 

  1. There are many observations about CBD having other interactions in other systems, even the opioid system. This is highly probable and in some cases already proven true. There is general acceptance that CBD is a most powerful agent to liberate arachidonic acid (AA) from the phospholipids in the cell plasma membranes. This acid is 20 carbons long and is a precursor for making eicosanoids, of which more than 150 have been identified. These are the signaling agents for most all biological operations. Half are synthesized endogenously from Omega 3 and half from Omega 6. It is believed the two sources represent opposing functions that rise in inflammatory and resolution phases of “eicosanoid storms”. Strong functioning of the eicosanoid system over a life time is essential for good long-term health.

 

  1. A very strong eicosanoid function is interacting with a wide range of molecular biology functions in our many biological operations.

 

The three systems: Opioid System, Cannabinoid System and Eicosanoid System, their agencies and how they work:

 

Exogenous Opioids induceneurotoxicity,this is damage to the nervous system including the brain. Exogenous opioid neurotoxins alter the activity and structure of the nervous system in ways that disrupt and even kill nerves. While Opioids do reduce pain, over time more and more is required to sustain an effect and this increases neurotoxin effects. Removing it causes hypersensitivity. Withdrawal. Pain. Cravings. Treating opioid detox with other opioids means neurotoxicity does not cease, it is not reversed, it goes on. A plan for failure.

 

CBD is involved inneurogenesis.  Neurogenesis is when nervous system cells, known as neurons, are produced by neural stem cells (NSC)s. Neurogenesis is most active during embryonic development and continues during our lifetime. Once formed neurons many will live one’s lifetime. Studies show that CBD increases the production of stem cells and this is an insight into its neurogenesis activity.

 

Since CBD is a very important contributor to the eicosanoid system it is likely able to enhance and optimize many biological operations, from pain mediation, to healing, inflammatory and anti-inflammatory responses and many others.  It releases arachidonic acid (AA), a critical precursor for making the eicosanoids from the Omega 3 and Omega 6 fatty acids. Eicosanoids are signaling molecules that appear to play across most all systems.  More than 150 different ones have been identified.

 

How to explain this? Let’s start with an understanding of the two systems. In this case it is best to quote an expert and include their citations: In Interactions of the opioid and cannabinoid systems in reward: Insights from knock out studiesKatia Befort as published in a review article published: 05February2015 doi: 10.3389/fphar.2015.00006 in Frontiers in Pharmacology:

The Opioid System: The opioid system consists of endogenous opioid peptides (enkephalins, endorphins, and dynorphins) from precursors (Penk, Pdyn, and Pomc) which activate three opioid receptors, namely mu, delta, and kappa (Kieffer,1995). The three membrane receptors, cloned in the early nineties (Evansetal.,1992; Kiefferetal.,1992; Simoninetal.,1994, 1995; Mesteketal.,1995) are GPCR with coupling to Gi/Go proteins, of which the 3D Structure was recently resolved (see FilizolaandDevi,2014). …Opioid receptors and endogenous opioid peptides are largely expressed throughout the nervous system, noticeably within areas of the neurocircuitry of addiction associated with reward, motivation, or learning and stress (Mansouretal.,1995; LeMerreretal., 2009; KoobandVolkow,2010; Erbsetal.,2014).

The Endocannabinoid System: The endocannabinoid system is a neuro modulatory system consisting of two well characterized trans membrane receptors coupled to G protein (Gi/Go), CB1, and CB2 cloned in the1990’s (Matsuda etal.,1990; Munroetal.,1993). The endogenous ligands are lipid neuromodulators, the main ones being AEA and 2-AG. Both are synthesized from phospholipid precursors and act locally as retrograde regulators of synaptic transmission throughout the central nervous systemThe endocannabinoid system plays a key role in energy balance, modulation of pain response, with processing of central and peripheral pain signals, learning and memory, reward and emotions. It has also been shown to be involved in neurogenesis and would play a neuro protective role in some pathological conditions.

While these systems seem to be operating in similar functions and pathways, only the ECS is involved in neurogenesis and modulation of pain response.

Dr. Befort goes on to write: Although the endocannabinoid system has been known to interact with other systems like hypocretin, dopaminergic, and adeno synergic systems (Fernandez-Ruiz et al.,2010; Ferreetal.,2010; Tebanoetal.,2012), its interaction with the opioid system is now well established.

Opioid Detoxification and CBD:

 

The US is suffering from a very dangerous opioid addiction epidemic. Remarkably, the gateway drug for many if not most current addicts have been and is opioids prescribed by medical doctors for pain management. In my recent essay on pain, I detailed how of the three classes of painkillers, opioids, non-opioids and adjuvants, opioids and non-opioids suffered from severe hazards and limits of efficacy, opioids’ dangers are well known, and acetaminophen is the cause of many fatalities from liver toxicity. And they both suffer from limited efficacy. So, I suggested in that essay that CBD should be considered the pain killer of choice for safety and efficacy.

 

We must recognize that opioid addiction is a neuropsychiatric disease.  These abusive substances interact with two neuro modulator systems, the opioid and the endocannabinoid

systems.  To overcome and “Cure” addiction we have to heal the brain. There is no evidence of a positive correlation between the power of an exogenous opiate’s psychoactive power and the power of the neurotoxicity to rearrange the opioid receptors. So, the current procedure of trying to wean addicts off powerfully psychoactive forms of opioids by giving then less psychoactive opiates may be increasing the neurotoxic effects of the opiates on the brain and making a cure of this addiction even less likely.

 

With this insight and understanding we make the suggestion that CBD is not just the best painkilling treatment for getting an opioid addict through detoxification, but also that CBD can be a very powerful agent to aid in the necessary healing and recovery of the opioid damaged brain.

 

Let’s start with the idea that the opioid damaged brain can be healed and aided in recovery. No less than Dr. Sanjay Gupta wrote to Attorney General Sessions making reference to Dr. Yasmin Hurd’s work, Director of the Addiction Institute at Mount Sinai in New York City: (https://www.cnn.com/2018/04/24/health/medical-marijuana-opioid-epidemic-sanjay-gupta/index.html)

 

“For the past 40 years, we have been told that cannabis turns the brain into a fried egg, and now there is scientific evidence that it can do just the opposite, as it did for Campbell. It can heal the brain when nothing else does.

Dr. Hurd showed me what this looks like in autopsy specimens of those who had overdosed on opioids. Within the prefrontal cortex of the brain, she found damage to the glutamatergic system, which makes it difficult for neural signals to be transmitted. This is an area of the brain responsible for judgment, decision-making, learning and memory.

Hurd told me that when an individual's brain is "fundamentally changed" and diseased in this manner, they lose the ability to regulate opioid consumption, unable to quit despite their best efforts -- unable to "just say no."

It is no surprise, then, that abstinence-only programs have pitiful results when it comes to opioid addiction. Even the current gold standard of medication-assisted treatment, which is far more effective, still relies on less-addictive opioids such as methadone and buprenorphine. That continued opioid use, Hurd worries, can cause ongoing disruption to the glutamatergic system, never allowing the brain to fully heal. It may help explain the tragic tales of those who succeed in stopping opioids for a short time, only to relapse again and again.

This is precisely why Hurd started to look to other substances to help and settled on non-psychoactive cannabidiol or CBD, one of the primary components in cannabis. Hurd and her team discovered that CBD helped "restructure and normalize" the brain at the "cellular level, at the molecular level." It was CBD that healed the glutamatergic system and improved the workings of the brain's frontal lobes.”

 

 

My conclusions:

 

  • CBD can be used to mitigate pain and heal the opiate damaged brain;

 

  • Using opiates of any form for detox, does not make much sense and may be counterproductive: it has a high probability of causing more damage to the brain;

 

  • CBD is not dangerous; it is safe.

 

  • CBD is not addictive;

 

  • Exogenous opioids are neurotoxins

 

  • CBD is involved in neurogenesis and helps heal the opioid damaged brain.

 

  • Industry and the government got all this badly, very badly, wrong.

 

  • The government has got things wrong in these and similar regards many, many times.

 

  • There are numerous peer reviewed references that suggest bioavailability of CBD can be enhanced by nano sizing and associating with nano sized constituents such as chlorophyll.

 

  • Most opiate addicts made their own decisions to use the opiates based on a change in their brains: they are sick, they need healing. Once addicting they are medicating. They need a better path out of addiction. Educating ourselves, and our communities and our loved ones currently comes not from our government or medical professionals or industry or agencies. They have all failed us. It falls upon ourselves. We will continue to study this and share information, science, data, insights and observations with the idea of helping to solve this problem and do maximum good.

  

Some suggested reading:

 

  • Nicole E Burma, Charlie HT Kwok & Tuan Trang Therapies and mechanisms of opioid withdrawal2217/pmt-2017-0028 C 2017 Future Medicine Ltd Pain Manag. (2017) 7(6), 455–459

 

 

  • CANNABIDIOL MITIGATES OPIOID REWARD ON CONDITIONED PLACE PREFERENCE IN MICE By: James Roland Markos A thesis submitted to the faculty of The University of Mississippi in partial fulfillment of the requirements of the Sally McDonnell Barksdale Honors College March 2017

 

  • Prud’homme et al. Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence. Substance Abuse: Research and Treatment 2015:9 33–38 doi: 10.4137/SART.S25081.

 

  • Thomas R. Kosten, M.D. Tony P. George, M.D. The Neurobiology of Opioid Dependence: Implications for TreatmentRESEARCH REVIEWS—THE NEUROBIOLOGY OF OPIOID DEPENDENCE • 13

 

  • Kerstin Iffland and Franjo Grotenhermen An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal StudiesCannabis and Cannabinoid Research Volume 2.1, 2017 DOI: 10.1089/can.2016.0034

To illustrate how this understanding and approach is being widely explored and even accepted and endorsed, I offer these references to the website of very active researchers and clinicians:

 

  • Dustin Sulak in Portland, Maine,

https://integr8health.com/

 

 

 

  • Julie Holland in New York City 

http://www.naturalmood.com/

 

  • Mark Wallace in San Diego

https://providers.ucsd.edu/details/11631/mark-wallace-anesthesiology-pain_management-san_diego

 

  • Sue Sisley in Phoenix.

http://www.medicalcannabis.com/about/faculty/suzanne-sisley/

 

  • WHO Reference and document on CBD file:///C:/Users/John/Desktop/snce/John's%20essays/Pain/WHO%202017%20on%20CBD.pdf

 

  • On bioavailability: Yumika OKADA, Masaharu ISHIKURA & Takashi MAOKA (2009) Bioavailability of Astaxanthin in Haematococcus Algal Extract: The Effects of Timing of Diet and Smoking Habits, Bioscience, Biotechnology, and Biochemistry, 73:9, 1928-1932, DOI: 10.1271/ bbb.90078

 

  • M.R. Meor Mohd Affandi, T. Julianto and A.B.A. Majeed Enhanced Oral Bioavailability of Astaxanthin with Droplet Size ReductionFood Sci. Technol. Res., 18 (4), 549 – 554, 2012

 

Respectfully and hopefully shared, John Carberry