Monthly Archives: July 2016

Petition leaves FDA Confused

In AFDAug of 2015 The Take Back America Campaign, an organization made up of Drug Free America people, filed a petition with the FDA to require labeling of Cannabis products.  The petition asked the FDA to “establish standards for “Medical” and “recreational” cannabis products.

The petition further states what they would like to see on the label and why.

They argue that CBD is a beneficial component and is known to mitigate the euphoria associated with THC.  However genetic manipulation of the plant by growers has increased the concentration of THC from 2.17% to almost 10% and the concentration of CBD has decreased from .24% to .008%  The potency has continue to climb dramatically since 2008.  Stating that “medical” marijuana sold in the normal range of 20% to as high as 37% in smoked form and as high as 96% as an extract or Oil.

NIDAThey further argue that Marijuana causes Physical and Mental problems including Cancer.  Relying on NIDA studies they also claim that Cannabis can cause: cancer of the Head, Neck, Bladder, Brain and Testis; cause chronic bronchitis and other respiratory problems and elevates the risk of heart attack.  They also claim it it is a major cause of strokes as well.  They further claim that Marijuana causes DNA damage resulting in mutations and chromosomal abnormalities that can affect future generations.  The list of things all debunked by science is long and if you wish to read it you can in the attached document.  Citizen_Petition_from_The_Take_Back_America_Campaign

They claim that there is “ample amount of scientific evidence and information available to request the FDA Commissioner to hold Public Hearings and open up a Federal Registry to establish standards and oversight of Marijuana, currently being marketed as a drug and food.”

imagesThey falsely claim there is no economic impact involved with the petition.  This is blatantly false, there would be significant economic impact if the purposed labeling requirements are implemented.  in order to determine what they are asking the FDA to require would be expensive for the existing businesses and people involved in the industry.  There would be further impact if they get the FDA to enforce the CSA, which is the domain of the DEA.

They are asking the FDA to:

  1. Determine standards for packaging, labeling, dosage, contents and potency of marijuana produced as medicine and food
  2. Create and implement an educational awareness program for all members of the public about the side effects and harms of marijuana
  3. Shut down or bring into compliance marijuana dispensaries that are selling marijuana products for medicine or recreation that do not comply with safe standards.
  4. Enforce federal CSA laws in all the states and bring them into compliance with federal law.

The FDA is not very happy with this petition and expresses it rightly in it’s reply to the Petitioners.  A copy of the FDA response is here – Citizen_Petition_Interim_Response_from_FDA_OP_to_Roger_Morgan,_Frederick_Mayer,_Ron_Allen,_Scott_Chipman

In it’s interim reply, of April 2016, they state that the “FDA has not yet resolved the issue raised in the citizen petition.”   The FDA reason why they have not been able to resolve the issue.  “it raises numerous and complex issues requiring extensive review and analysis by Agency officials.”

This is obvious that it raises “numerous and complex issues” for the FDA.  If the FDA determines that there needs to be standards for packaging, labeling, contents of marijuana, they are making a statement about Marijuana.  If they require dosage and potency to be in the label they are calling Marijuana a recognized drug.  If they attempt to bring people into compliance with the CSA they are stepping into the area that is controlled by the DEA.

The public, members of the industry and others are encouraged to comment on the petition at the following link.

****NOON UPDATE****

PLEASE THINK CAREFULLY BEFORE RESPONDING TO THE PETITION.

There are upsides to having FDA recognize that Cannabis is a product and require labeling.

There are also downsides to having FDA labeling.  Especially if those that are asked for in the petition are given.  It would be likely that IF FDA were to decide to require labeling that some sort of middle ground would be met.

http://www.regulations.gov/docket?D=FDA-2015-P-3991

 

Confused you will be, THC is Schedule I, III and Not

According to Sigma-Aldrich, THC and other Cannabinoids are not only in Schedule I, III but also unscheduled as well.

pubchemlogo_2015I know I was and still am a little confused.  It all started with a search of the federal government Medications database for Cannabinoid.  PubChem lead me to what I already expected to see Marinol/drobininol the synthetic THC that is prescribed to cancer patients.

hgDPF-j4_400x400I also found that a number of other cannabinoids were already in the database.  Cannabinol, and a variety of analog cannabinoids.  Many of them being manufactured by Sigma-Aldrich.  Sigma became a subject of search to see what they offered and what they offered amazed me to say the least.

The ease of use of their website is amazing and the information very revealing.  The most revealing is that you can purchase THC, and other cannabinoids without any license from the DEA.  According to the company because they are “in a solution of methanol and at a concentration of 1mg/ml they are exempted from DEA license.”  Yet other THC and Cannabinoids that are in Ethanol are on Schedule I according to them.  According to information from the DEA THC that is in Sesame Seed Oil is a schedule III substance.  How can THC be in 2 schedules and also not in any schedules?

This seems rather bizarre because of the concentration is 1mg/ml they are exempt from the CSA.  As a former Navy Medic and father of a RN soon to become a NP, this didn’t seem correct.  In medicine a dose is prescribed, not a concentration.

The concentration of the dose is only relevant to the dose prescribed.  If 1mg of something would be prescribed.  Manufacturers might not make a 1mg size instead making a 0.5mg or 2mg dose in which case the amount of the medication might be adjusted.  If the amount in a tablespoon is 0.5mg and the prescribed amount is 1mg a person simply takes two tablespoons to get the prescribed dose.  The concentration of the medication is only relative to the amount of medication in the form prescribed and the prescribed dosage.

DEASo why does it matter what the concentration of a cannabinoid is that can take it from being a Schedule I substance to a unscheduled substance?  This is the conundrum of DEA logic when it comes to Cannabis and Cannabinoids.  They seem to be hung up on concentrations of a substance within another substance which is irrelevant to the heart of the CSA.

The heart of the CSA is to Control Substances, and Prevent Diversion.  A substance is either on the schedule or it isn’t, at least any other substance is.  Codeine, Cocaine, Opiate derivatives are on the CSA in all concentrations, there is no magic concentration that suddenly it’s controlled.  Every other substance on the CSA is controlled in it’s entirety, regardless of “concentration” but not Cannabis and Cannabinoids.

hempSo what’s going on?  Part of it is a case against the DEA brought by HIA which forced DEA to exempt certain products made from Cannabis that might contain small percentages of cannabinoids of various types in very low amounts.  Another is the passage of the Farm bill which allowed for the production of Cannabis for commercial products.  The thought being that low Cannabinoid varieties could be grown by farmers.

The flaw is that concentrations of one Cannabinoid vs others is relative to the other cannabinoids.  Conversations with the Bast Fiber Institute in the Ukraine and The University of Minnesota is that cannabinoid levels are related to each other.  As THC goes down other cannabinoid levels rise.  So you can have low THC producing cannabis but it will produce a greater amount of other Cannabinoids.  This leads to the inevitable circle of you can’t grow a plant with one concentration of any cannabinoid being above a certain level.  Something that simply can’t be attained.

Back to the main subject that some “concentrations” of Cannabinoids are legal.  What could be done with them?  First they are in methanol, not a safe substance to ingest so I wouldn’t suggest you order up a bunch.  Also as soon as you change the concentration they become a controlled substance again.  They are research chemicals and not prescribable by physicians.  Yet there they are, out there for sale, legally without any controls by the DEA.  It simply doesn’t make any sense but when it comes to Cannabis it never does seem to make any sense.

Watching Social Media for Cannabis Use

big-brotherUnder a grant from NIDA, Wright State University is going to develop software that will allow someone to monitor social media for Cannabis use and more.

According to the Description they explain that “Cannabis remains one of the most commonly used psychoactive substances in the U.S., and current changes in legalization policy indicate broadening acceptability. At the same time, substance abusers have sought similar, or more enhanced highs, through use of synthetic cannabinoids, new designer drugs with constantly changing chemical formulations that have been linked to adverse health effects and present significant challenges to public health.”

Remarkably it’s clear that NIDA assumes that Cannabis legalization leads to other drug use when so many studies in states that have legal cannabis shows the opposite.  Despite this apparently NIDA is determined to stay on top of this and maybe other things with the development of the software they are funding research into.

With it’s $461,000 funding from NIDA they purpose to  “Develop a comprehensive software platform, eDrugTrends, for semi-automated processing and visualization of thematic, sentiment, spatio-temporal, and social network dimensions of social media data (Twitter and Web forums) on cannabis and synthetic Cannabinoid use.”

Once the software is developed it’s very easy to put in whatever you want to have found out.  This could have chilling effects on all sorts of issues.  You will note that they want to use this software to Identify Key Influencers and explain them to be “Opinion Leaders”

Then they plan to “Deploy eDrugTrends to: a) Identify and compare trends in knowledge, attitudes, and behaviors related to cannabis and synthetic Cannabinoid use across U.S. regions with different cannabis legalization policies using Twitter and Web forum data. b) Analyze social network characteristics and identify key influencers (opinions leaders) in cannabis and synthetic cannabinoid-related discussions on Twitter.”

heat1Once deployed there will be no stopping this invasion into cyberspace of basically a search engine that monitors and gives visualization of what is trending.

The development of eDrugTrends will advance the field’s technological and methodological capabilities, and our deployment of the platform will inform the field on new trends regarding the use of cannabis, synthetic cannabinoids and other drugs. eDrugTrends will have high public health impact by providing a tool that can be used to inform more timely interventions and policy responses to changes in cannabis and synthetic Cannabinoid use and associated harms.”

NIH RePORTS – LINK

They have already deployed the software and articles are appearing like the following in PubMed

“Those edibles hit hard”: Exploration of Twitter data on cannabis edibles in the U.S.

“Our findings suggest that Twitter data analysis is an important tool for epidemiological monitoring of emerging drug use practices and trends.”
“Although the majority of tweets conveyed positive attitudes about cannabis edibles, analysis of experiences expressed in negative tweets confirms the potential adverse effects of edibles and calls for educating edibles-naïve users, improving edibles labeling, and testing their THC content.”

Making Cannabinoids from Yeast?

wss_skunk_cured_budYet another Pharmacutical Company is investing in Cannabinoid medications and production.  Librede has developed a method to produce Cannabinoids from glucose.    In NIH RePORTS there is a study being done under National Center for Complementary & Integrative Health (NCCIH) of the National Institutes of Health (NIH) along with Librede to make cannabinoids using yeast instead of the plants.

They argue..

0349fe3“Cannabinoids can be found in many plants, the most well-known is Cannabis sativa, but, like many other natural products that have been developed into pharmaceuticals, the production of most of these compounds by the plant are at low levels. The difficulties in sourcing these Cannabinoids inhibits Research and makes their eventual development and production into pharmaceuticals problematic.

To increase the accessibility as well as our basic knowledge of Cannabinoids and enable the pursuit of natural Cannabinoids as Therapeutic agents, Librede has developed a biosynthetic Cannabinoid production/drug discovery platform based on genetically engineered yeast with selected portions of Cannabis sativa metabolic pathways.

image012The production of Cannabinoids in yeast is an ideal platform because fermentation and genetic engineering are well-established, low cost, and scalable. Since we can choose to engineer yeast strains to produce only a single Cannabinoid, the effort and cost of separation/purification are minimized. Furthermore it is a modular platform technology-by adding or removing expression of different enzymes, different Cannabinoids can be produced as desired, even Cannabinoids produced in low abundance naturally.”

“In order to increase the yield to provide compounds for early testing and to prepare for large scale production Librede has developed a method to produce Cannabinoids from glucose. In the work proposed here, we will add the published glucose→hexanoic acid pathways to our yeast allowing for the production of CBDA from glucose.

The platform is modular and can be used to create a wide range of natural Cannabinoids. By swapping out the last enzyme in the biosynthetic pathway (e.g change CBDA synthase to CBCA synthase) different Cannabinoids can be produced. As a result, we will have a modular, high yield platform for synthesis of specific natural Cannabinoids from glucose which is scalable for production of compounds at levels suitable for basic Research, clinical trials, and for Therapeutic use. ”

PUBLIC HEALTH RELEVANCE Cannabinoids are natural products with the potential to treat a wide range of diseases, but most are expressed in plants in very low levels, making their production and extraction highly uneconomical. Librede has developed the world’s first in vivo biosynthetic platform for Cannabinoid production from genetically engineered yeast. We propose to enable practical production with our platform by engineering the yeast to use glucose as a feedstock.

Link To NIH RePORTS information – LINK

Information as of July 2016 – 1R43AT009151-01

Librede News report about Cannabinoid Research – LINK

 

Aphios Corp Developing New Manufacturing Process

NIHInformation found in a search of the public NIH database for Therapeutic Cannabinoid Research has turned up an interesting project that is underway.

A new way to make Cannabinoid Medications, including THC, that use the Cannabis Plant as it’s source.

Funded with $1 Million from NIDA, this is kind of surprising.  First the company has had a license to make these substances since 2002 from the DEA and second that NIDA is sponsoring this research.

It is clear that with this research project and the ones being done in secrete by Sigma-Aldrich Pharmaceutical companies see money in Cannabis based medications.

NIDA“The primary goal of this Research program is to develop a process for manufacturing pharmaceutical grade CBD following current Good Manufacturing Practices (cGMP) of the US FDA for use in clinical trials for childhood epilepsy and other CNS indications by the NIH and other Researchers.”

Going even further to say that they can make this from the Cannabis Plant.

We hypothesize that CBD and CW can be cost-effectively manufactured from high CBD content wss_skunk_cured_budCannabis sativa (hemp) utilizing supercritical fluid technology, and that such a process could also produce other bioactive Cannabinoid mixtures for future Research and Therapeutic use. We propose to manufacture pharmaceutical-grade CBD (>98.5% and < 0.3% Δ9-THC) and a standardized CW fraction (30% CBD and < 0.3% Δ9-THC) both following cGMP guidelines by utilizing supercritical fluids and near- critical fluids with or without polar co-solvents such as alcohols (SuperFluids¿). These fluids are gases such as carbon dioxide which when compressed, exhibit enhanced thermodynamic properties that can be “fine-tuned” for rapid and selective extraction of bioactive molecules. We will obtain sufficient quantities of high CBD content Cannabis sativa from growers in Colorado, Maine or Massachusetts and/or NIDA to conduct the proposed Research.

hempThey add  “Under the newly passed Farm bill, recently signed by President Obama, the farming and intra-state transportation of hemp (< 0.3% Δ9-THC) are now exempt from the Schedule 1 requirements of the Drug Enforcement Agency. Since 2002, Aphios has been an approved Schedule 1 Research facility with DEA license No. RC0288058 to Research and develop DEA Schedule 1 products.

Going further they state “The legitimate use of marijuana for several medical indications has far outpaced the medical and Clinical Evaluation of marijuana and specific Cannabinoids for different medical uses. In 1997, the National Institutes of Health convened an Ad Hoc Expert Panel to discuss current knowledge of the medical uses of Cannabis. The report discussed the importance of other Cannabinoids and their potential interaction effects upon THC, stating: “Varying proportions of other Cannabinoids, mainly cannabidiol (CBD) and cannabinol (CBN), are also present in Cannabis, sometimes in quantities that might modify the pharmacology of THC or cause effects of their own. CBD is not psychoactive but has significant anticonvulsant, sedative, and other pharmacological activity likely to interact with THC.” The Institute of Medicine (IOM, 1999) concluded that scientific data indicate the potential Therapeutic value of Cannabinoid drugs, primarily Δ9-THC, for pain relief, control of nausea and vomiting, and appetite stimulation and clinical trials of Cannabinoid drugs for symptom management should be conducted.”

adding “We propose to manufacture pharmaceutical-grade CBD for Clinical Evaluation by the NIH and other pharmaceutical companies for Multiple Sclerosis and other CNS diseases, and a standardized Charlotte’s Web (CW) product for use by medical marijuana dispensaries in Massachusetts and other states for childhood epilepsy.

“PUBLIC HEALTH RELEVANCE: The legitimate use of marijuana for several medical indications has far outpaced the medical and Clinical Evaluation of marijuana and specific Cannabinoids for different medical uses. In 1997, the National Institutes of Health convened an Ad Hoc Expert Panel to discuss current knowledge of the medical uses of Cannabis. The report discussed the importance of other Cannabinoids and their potential interaction effects upon THC, stating: “Varying proportions of other Cannabinoids, mainly cannabidiol (CBD) and cannabinol (CBN), are also present in Cannabis, sometimes in quantities that might modify the pharmacology of THC or cause effects of their own. CBD is not psychoactive but has significant anticonvulsant, sedative, and other pharmacological activity likely to interact with THC.” The Institute of Medicine (IOM, 1999) concluded that scientific data indicate the potential Therapeutic value of Cannabinoid drugs, primarily Δ9-THC, for pain relief, control of nausea and vomiting, and appetite stimulation and clinical trials of Cannabinoid drugs for symptom management should be conducted. We propose to manufacture pharmaceutical-grade CBD for Clinical Evaluation by the NIH and other pharmaceutical companies for Multiple Sclerosis and other CNS diseases, and a standardized Charlotte’s Web (CW) product for use by medical marijuana dispensaries in Massachusetts and other states for childhood epilepsy. “

Link to current information on NIH RePORTS system – LINK

Current information as of July 2016 – 4R44DA038932-02

 

Cannabis the next Penicillin?

hgDPF-j4_400x400The Antibacterial cannabinoids from Cannabis sativa are well known to Sigma-Aldrich.  As any good pharmaceutical company they are looking at the antibacterial properties of all 5 known cannabinoids.

A report they have available on their website promoting their version of Dronabinol, which is actually available as a solution rather than a pill form and according to them is a Schedule I substance.

“Marijuana (Cannabis sativa) has long been known to contain antibacterial cannabinoids, whose potential to address antibiotic resistance has not yet been investigated.”wss_skunk_cured_bud

As any good pharmaceutical company they are actively researching to find the MAGIC combination of the hundreds of compounds naturally found in Cannabis.  Obviously if they can find even part of the magic combination found in nature they can have a very powerful antibiotic that will treat even MRSA or so is the claim in an article that was published in 2008 in Journal of Natural Products.

All five major cannabinoids (cannabidiol (1b), cannabichromene (2), cannabigerol (3b), Delta (9)-tetrahydrocannabinol (4b), and cannabinol (5)) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance.”

Could Cannabis be the next Penicillin?  If Sigma-Aldrich has their way yes and they will own it.

 

** NOTE** We have tried to get confirmation or denial from Sigma-Aldrich but no one is able to answer the question.

Cannabinoids Treatment for MRSA?

hgDPF-j4_400x400Antibacterial cannabinoids from Cannabis sativa: a structure-activity study.  Sigma-Aldrich is looking at the antibacterial properties of all 5 known cannabinoids.

“Marijuana (Cannabis sativa) has long been known to contain antibacterial cannabinoids, whose potential to address antibiotic resistance has not yet been investigated.”

“All five major cannabinoids (cannabidiol (1b), cannabichromene (2), cannabigerol (3b), Delta (9)-tetrahydrocannabinol (4b), and cannabinol (5)) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance.”

Here is a link to the entire article that was published back in Journal of Natural Products 2008-08-01 –  LINKAntibacterial cannabinoids from Cannabis sativa: a structure-activity study. | Sigma-Aldrich