Tag Archives: pharmacology

DEA says Inhaled is Better

Today the DEA announced that they have a new FDA approved form of THC called Syndros.  Syndros is the result of work of Insys Therapeutics to create a new oral THC that has 5mg per ML of solution. – FEDERAL REGISTER LINK

In the DEA’s findings they are planning to schedule this as a Schedule II drug because.

Dronabinol is a generic name for the (-) delta-9-trans isomer of tetrahydrocannabinol (THC). THC is the primary psychoactive substance in marijuana. Dronabinol is the active pharmaceutical ingredient in Syndros. As stated by HHS, Marinol (synthetic dronabinol in sesame oil and encapsulated in a soft gelatin capsule) was approved by the FDA for medical use on May 31, 1985 and placed in schedule II based on its accepted medical use and high abuse potential. On July 2, 1999, Marinol was rescheduled from schedule II to schedule III because of the findings of the DEA that the difficulty of separating dronabinol from the sesame oil formulation and the delayed onset of behavioral effects due to oral route administration supported a lower abuse potential of Marinol as compared to substances in Schedule II. 64 FR 35928.

Going on to state:

HHS indicated that the formulation of Syndros (oral solution) is easier to abuse than Marinol because this liquid formulation can be manipulated to produce concentrated extracts of dronabinol for abuse by inhalation (smoking or vaping) or through other routes of administration. Because of the large amount of dronabinol in Syndros oral solution it has a greater potential for extraction than Marinol and thus has a greater abuse potential.

Based on the use of Cannabis by the general public DEA feels that this form of THC needs to be a Schedule II drug.

What you find when reading further down is that it appears DEA would rather people smoke it because of the onset of effects are easier to control.

Oral consumption of dronabinol, compared to inhaled THC, may result in psychoactive effects that are delayed and stronger with an increased risk of experiencing serious adverse events.

But then they quickly add:

When dronabinol (THC) is smoked, the drug rapidly reaches the brain and psychoactive effects are felt within minutes of inhalation, which allows the subject to control the dose more readily.

The DEA is full of contradictory things but this just about takes the cake.  Using a substance via oral methods pose issues that smoking or inhalation don’t and is better at controlling the dose.  However they are afraid that people will do just that.  Take this new drug and turn it into something they can control the dose better.

There is a time that this potential rule can be commented on, see the link at the top of the page to the federal register.

VA releases Medical Cannabis Report

If anyone has been watching the VA website they had a report about the medical use of Cannabis for Pain and PTSD.  The document has not been available for the public but through the power of the Freedom of Information Act we were able to get a copy.

This 124 page, well researched document is probably one of the most extensive looks at Cannabis done by a Government agency.  It not only looks at the use of Cannabis for Pain and PTSD but also looks at the harms of Cannabis use.

While they didn’t find much quality research on the medical use of Cannabis for Pain or PTSD they did find a lot of information.  The research they cite from all kinds of sources indicate that the lack of research is limiting their ability to make quality decisions on Cannabis for Medicine or Safety.

CONCLUSIONS

Although cannabis is increasingly available for medical and recreational use, there is very little methodologically rigorous evidence examining its effects in patients with chronic pain or PTSD. There is limited evidence that cannabis may be helpful in improving pain and spasticity in selected populations with MS, but there is insufficient evidence in other populations. There is insufficient evidence examining the effects of cannabis in PTSD populations. Cannabis is associated with an increased risk of short-term adverse effects, but data on its effects on long- term physical health vary; harms in older patients or those with multiple comorbidities have not been studied. Cannabis has been associated with short-term cognitive impairment and potentially serious mental health adverse effects such as psychotic symptoms, though the absolute risk and application specifically to chronic pain and PTSD populations are uncertain.

You can get the entire document here at this link – Benefits and harms of cannabis in chronic pain or post traumatic stree disorder

Cannabis Extract Opens New Door

Everyone is talking about how terrible it was of the DEA to create a number for Cannabis Extracts.  Well there is an upside to the situation.

All the attention is being made to the single mention of CBD being made a Schedule I substance.  Nothing is further from the truth, CBD is not a scheduled substance by the federal government.  NO Cannabinoid, with exception to THC, is a controlled substance according to the federal government.

What has been missed by everyone is the DEA’s statement about CBD extracted from the Cannabis Plant.  That they see no way for it to be extracted without extracting other Cannabinoids like THC which is a scheduled substance.   So there is no change in the stance of the DEA, there has actually been clarification that mixtures of CBD that contain THC and are extracted from the cannabis plants are extracts, those without are not.

What people have been missing is the opportunity to petition the DEA to De-schedule Extracts.  As extracts now have their own ID number they can be scheduled differently than Cannabis just as THC is scheduled differently.

The science is clear and evident that Extracts are by far safer than raw cannabis.  It’s easier to maintain dosage and test lots.  You can take a ton of cannabis and create and extract, test that batch for purity and level of cannabinoids and have a uniform product.  Unlike a plant which changes from plant to plant, even if cloned, extracts offer uniformity which is what the FDA likes.

Extracts make sense and it makes sense to De-schedule them or Re-schedule them into another schedule like THC has.

DEA and Marijuana Extract Means.. NOTHING

On Dec 14th the DEA announced a new drug code for “Marijuana Extract” and there has been a lot of furor over the decision.  For those that have read the CSA and understand the meaning of the definition of “Marijuana” it already meant:

The term “marihuana” means all parts of the plant Cannabis sativa L., whether growing or not; the seeds thereof; the resin extracted from any part of such plant; and every compound, manufacture, salt, derivative, mixture, or preparation of such plant, its seeds or resin. Such term does not include the mature stalks of such plant, fiber produced from such stalks, oil or cake made from the seeds of such plant, any other compound, manufacture, salt, derivative, mixture, or preparation of such mature stalks (except the resin extracted therefrom), fiber, oil, or cake, or the sterilized seed of such plant which is incapable of germination.

Prior to this announcement everything other than THC, which already has it’s own drug code, all other Cannabinoids were classified under the Marijuana Code.  What this does is separate out for purposes of clerical and data collection a difference between raw Cannabis plant material and Extractions made from the plant.

NOTHING has changed, no substance scheduling has changed, no laws have been changed.

So what does it really mean?  What it really means is that now the extracts that researchers have been getting from the Mississippi Farm now have a separate code.  This allows the DEA, FDA, HHS, NIDA to track what kind of research is being done.  Is it whole plant or an extract that is being used.

Frankly it wouldn’t be a bad idea to put each cannabinoid it’s own drug code.  This could do two things.  First it would track what research is being done with what cannabinoids.  It could also lead to many more cannabinoids being put into different schedules like THC is in a different schedule.  One by one move the cannabinoids to other schedules and you less reason to keep the whole plant scheduled in schedule I

 

Pharmacists want more information

pmcIn a First of it’s kind study posted to PubMED shows that pharmacists want more information about medical cannabis.   The study conducted in Minnesota prior to Minnesota’s medical Cannabis program implementation shows that Pharmacists want more information on medical cannabis.  The Study was done by Joy Hwang, PharmD, MPH, Tom Arneson, MD, MPH, and Wendy St. Peter, PharmD

First the report determines that Minnesota Pharmacists, in general, have limited Knowledge of cannabis polices, regulations and felt they were not adequately trained.

Pharmacists reported limited knowledge of Minnesota state-level cannabis policies and regulations and felt that they were inadequately trained in cannabis pharmacotherapy. Most pharmacists were unprepared to counsel patients on medical cannabis and had many concerns regarding its availability and usage. Only a small proportion felt that the medical cannabis program would impact their practice. Pharmacists’ leading topics of interest for more education included Minnesota’s regulations on the medical cannabis program, cannabis pharmacotherapy, and the types and forms of cannabis products available for commercialization.

Unlike most states which have legal medical Cannabis Minnesota and a couple others have Licensed Pharmacists as the dispensers.  However in Minnesota these pharmacists are trained by their respective companies and have a great deal of knowledge about Cannabis use for medical purposes.

In these three states, pharmacists provide registered patients with consultations at one of the state-approved cannabis distribution centers. Moreover, they are the only health care professionals who are permitted to dispense cannabis products. This distinguishes these states from most other legalization states, where cannabis products—both medical and recreational—can be purchased from retail dispensaries that operate under the guidance of certified personnel known as “budtenders.”

The study was done to assess gaps in knowledge and concerns of Minnesota pharmacists.  The study conducted voluntarily via a web-based survey and had a 10% response rate by the states Pharmacists. The questionnaire had 14 questions they asked the pharmacists and also room for them to put in their own comments.

The majority of the respondents completed the survey and reported little concern about medical cannabis.

Most pharmacists rated themselves on the lower end of the Likert scale for self-perceived knowledge about medical cannabis and readiness to counsel patients on medical cannabis use (1 = poor; 7 = excellent) and concerns about medical cannabis use under the Minnesota program (1 = no concern; 7 = most concern)

Almost 90% of the respondents responded that they were less than moderately prepared to provide counseling services to patients using cannabis for medical purposes.

Pharmacists in general want more education.  This survey is of all pharmacists registered in Minnesota. Of those only a small number of them actually work with cannabis patients in the clinics that are available.  However it’s clear from this study that they want more education on Cannabis.

Respondents were very interested in learning more about medical cannabis in the following areas: state-specific rules and regulation (87%), pharmacotherapy (88%), and available types and forms of products on the market (82%). Fifty-three percent were interested in learning more about federal laws related to marijuana. Only 7% indicated no interest in learning more about any of these topics.

The study was conducted 2 months prior to Minnesota implementation of it’s cannabis program and there was a great deal of confusion about it.  Since the time of the survey information from a variety of sources including educational presentations to many hospitals, clinics, and hospital-clinic organizations in Minnesota with pharmacists as part of the audience, The University of Minnesota College of Pharmacy, Medical School and School of Nursing, full-day educational symposium on medical cannabis in April 2016, the Minnesota Pharmacists Association (MPhA) and the Minnesota College of Clinical Pharmacists.

The Study Concludes:

This study suggests that Minnesota pharmacists were not sufficiently prepared to work with patients in the medical cannabis program. Of those who provided survey responses, an overwhelming majority felt incompetent in medical cannabis clinical knowledge; however, almost half were unconcerned about the potential impact the program’s implementation would have on their practice. Nonetheless, pharmacists were interested in learning about medical cannabis and its state-specific regulation. Targeted education regarding cannabis pharmacotherapy, product availability and variability, and state-specific regulations should be available for health care professionals practicing in states with medical cannabis programs prior to program implementation and patient access.

 

Link to the study here – LINK

Copy of the study here – minnesota-pharmacists-and-medical-cannabis_-a-survey-of-knowledge-concerns-and-interest-prior-to-program-launch

 

WHO Pre-review Report Cannabis and Cannabis resin

With the upcoming meeting of the World Health Organization (WHO) Expert Committee on Drug Dependence Thirty-eight Meeting in Geneva, on 14 – 18 November 2016 many are calling for Cannabis to be an agenda item.

coverIn a pre-view Report “Cannabis and Cannabis Resin Pre-Review Report A document prepared for the World Health Organization” was prepared by H. Valerie Curran, Philip Wiffen, David J. Nutt, Willem Scholten.  In their report they give all the reasons why Cannabis should be more than an Update Item on the agenda.

In their report to the WHO they state in the preface:

In the eighty years since cannabis and cannabis resin were last reviewed by the Health Committee of the League of Nations in 1935, both the social context of cannabis use and the science of drug dependence have dramatically changed. Yet, cannabis and cannabis resin continue to remain under the strictest control regime possible under the Single Convention, without a valid scientific re-assessment of this decision. Cannabis and cannabis resin are listed in Schedule I and Schedule IV respectively, which means that both remain strictly prohibited worldwide.

then adding that the WHO is acting in a manner that appears to make continued prohibition illegitimate

The current scheduling of cannabis is in marked divergence with the Convention’s principle that scheduling of substances should be based on a scientific assessment by WHO. In the absence of a recent assessment, the continued prohibition of cannabis appears completely illegitimate even though it may be legal.

38ccdThey then proceed to ask the WHO to conduct a Scientific Review of cannabis and cannabis resin

A scientific review by the WHO, the only authoritative global body to make such an assessment, would greatly legitimize international policies and their national implementation. A scientific assessment of cannabis and cannabis resin appears most timely given the many debates that have emerged on this issue across the world in recent years.

In the fifty years since it’s inception the WHO has never conducted a scientific review of cannabis.  Despite it’s mandate to review the substance.

The scheduling under the Single Convention on Narcotic Drugs assumes a scientific justification. However, cannabis and cannabis resin have never been evaluated by WHO since it was mandated the review of psychoactive substances in 1948.

The purpose of the pre-review report is to clarify the position of the current state of use both medically and none medically.

The purpose of a Pre-review is to determine whether current information justifies a Critical Review. For evaluating substances in a Pre-review, the categories of information are identical to those used in Critical Reviews. At the stage of the Pre-review, the Expert Committee must decide whether the information justifies a Critical Review. If it finds that the data available may justify changing the scheduling of cannabis and/or cannabis resin, the Committee should recommend a Critical Review in its next Meeting.

The 53 page report, or 75 with cites, covers everything from adverse reactions, LD50 level, and pretty much everything you ever wanted to know about cannabis and how it works.  The report is remarkable in it’s completeness.

Conclusions Despite that the scheduling system of substances under the Single Convention on Narcotic Drugs is supposed to be based on scientific assessments, the WHO has never reviewed cannabis and cannabis resin. This means also that the Expert Committee continues to recommend that cannabis is not to be used medically despite growing evidence of considerable medical use world-wide, including the availability of a pharmaceutical preparation with a marketing authorization in multiple countries. Many countries are struggling with the impact of the prohibition of cannabis with its wide negative impact on societies (including through human rights violations) and on drug markets and drug use, including on the market of synthetic cannabinoids.

Committee recommendations are needed on the following topics:

1. Whether a Critical Review should be conducted for reviewing the current scheduling in Schedules I and IV. Each of the following reasons would justify a recommendation for a Critical Review: a. because WHO has never conducted a Critical Review, meaning that there is no scientific justification for the current scheduling; b. because the wide-spread medical use, including the use of preparations with a marketing authorization is in contradiction to listing in Schedule IV; c. because it is not clear whether the dependence-producing properties of cannabis and cannabis resin are between codeine and morphine (justification for Schedule I) or between dextropropoxyphene and codeine (justification for Schedule II) or below those of dextropropoxyphene (justification for not scheduling).

2. On the medical use of cannabis and its preparations (which can include revoking old recommendations by the Committee)

3. On the need of quality control on cannabis and cannabis products for medical and non-medical use.

Here is a link to the piece – LINK

Here is the report itself just in case it disappears from the net – whocannabisreport

Therapeutic Cannabinoid Research

Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues

marijuana-001In an article in Front. Pharmacol., 14 September 2016 Ethan Budd Russo the Medical Director of PHYTECS wrote extensively about the “Controversies” and in this article we will summarize some of the most important parts.

Among his many outstanding accomplishments we copy from his BIO

Ethan Russo, MD, is a board-certified neurologist, psychopharmacology researcher, and Medical Director of PHYTECS, a biotechnology company researching and developing innovative approaches targeting the human endocannabinoid system (“ECS”). The PHYTECS team pioneered scientific understanding of how the ECS regulates physiological functions including immunity, pain, inflammation, mood, emotion, learning, memory, metabolism, appetite, weight, sleep, embryo development, neuroprotection and stress responses.

Previously, from 2003-2014, he served as Senior Medical Advisor, study physician and medical monitor to GW Pharmaceuticalslogo for several Phase II and Phase III clinical trials of Sativex® for alleviation of cancer pain unresponsive to optimized opioid treatment, a Phase II study of Sativex to treat spasticity in cerebral palsy in children, various Phase I studies of Sativex drug abuse liability, and its effects on QTc interval and administration to patients with hepatic impairment, and Phase II studies of Epidiolex® for intractable epilepsy in children.

He graduated from the University of Pennsylvania (Psychology) and the University of Massachusetts Medical School, before residencies in Pediatrics in Phoenix, Arizona and in Child and Adult Neurology at the University of Washington in Seattle. He was a clinical neurologist in Missoula, Montana for 20 years in a practice with a strong chronic pain component. In 1995, he pursued a 3-month sabbatical doing ethnobotanical research with the Machiguenga people in Parque Nacional del Manu, Peru. He joined GW as a full-time consultant in 2003.

He has held faculty appointments in Pharmaceutical Sciences at the University of Montana, in Medicine at the University of Washington, and as visiting professor in the Chinese Academy of Sciences and Harvard Medical School.

It can be pretty much said that his creds are above reproach and he isn’t an anti Cannabis researcher, but he isn’t a pro smoking Cannabis supporter either.

In his 20 page report which you can get here he touches on just about everything. He also hold no punches as in his opening comments he states

Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents.

He does however make a mistake in his statement below.  There is no need for Cannabis to go through any approval process.

s there a pathway that will lead to the return of cannabis to mainstream medicine? The answer is clear, inasmuch as it has already commenced. It follows the same time-honored process that any pharmaceutical must attain to receive regulatory approval: proof of biochemical uniformity and stability along with safety and efficacy as proven by randomized clinical trials (RCT).

Unless sales occur in which case only testing for other issues should be addressed.  Cannabis has already proven itself to be safe, even varieties that produce large amounts of THC and other Cannabinoids. If it wasn’t safe you would see people dying in the streets from overdoses.  They do not even really show up in the Emergency Room, except for paranoia attacks and that has more to do with being worried about being arrested.

While he makes great comments about what would need to happen for Prescription type Cannabis they simply aren’t necessary given the safety of the product.  One thing he does address, not nearly enough emphasis is:

The biochemical variability of one chemovar to another is a primary challenge, while unregulated material may harbor pesticide residues, molds, bacteria, or heavy metals that endanger public health.

There does seem to be some sort of problem with people feeling good.  Not just releiveing a symptom but actually feeling better.  Which frankly seems at odds with all the other medications they shove down people to make them feel better.

In reality, patients are not seeking altered states from their medicine, but rather relief of pain or other complaints. Other cannabis-based medicines that follow will necessarily be required to meet similar benchmarks.

The problem with the current state run systems are a very real and possible source of a problem.

The singular controversy in this category is quality control. Short of a biochemical analysis by a certified laboratory employing verified phytocannabinoids standards, the cannabis consumer can have no real idea of the composition or consistency of the product that they purchase.

Labs that are doing testing may not be competent to test properly

The problem is compounded by the facts that technically almost all laboratories pursuing phytocannabinoid analyses in the USA are doing so illegally, most without benefit of a Schedule I license from the Drug Enforcement Administration (DEA). Additionally, many phytocannabinoid standards available commercially are reportedly suspect. There is additional difficulty in attempting to analyze cannabis confections, as the assays require ascertainment of cannabinoid content from a complex food matrix

He makes perfect sense when he states further in his paper

The author believes that full cannabinoid and terpenoid profiles are necessary for proper decisions by consumers in both the medical and markets

Can Cannabis as a plant be a medicine the Doctor seems to think so.  As he notes other plants have FDA approval and Cannabis has approval in other countries.  Adding:

Botanical medicines can even meet rigorous requirement of the American FDA as has already occurred for one topical agent (Veregen®, an extract of green tea, Camellia sinensis), and one single component botanical isolate taken internally, Fulyzaq® (crofelemer, from Croton lechleri). These approvals were achieved by following a blueprint that was updated in August 2015

FDAHere is a link to the FDA guidelines he speaks about – FDA

While he makes additional good points he misses that for over 10,000 years Cannabis has been used safely so passing any of these tests should be a simple matter.

If components of an extract are not already “Generally Recognized As Safe” (GRAS), clinical trials, safety-extension studies and rigorous quality control requirements all must be met. A botanical agent administered by a non-oral route, such as inhalation, requires additional pharmacology and toxicology documentation before initiation of RCTs.

What about kids?  Won’t they want to smoke Cannabis if they see others? NO according to the Doctors report.

The press frequently criticizes medicinal cannabis on the basis that acquiescence to its availability promotes usage by youth. To the contrary, analyses such as that undertaken by the US Government Accounting Office (GAO) reveal no increase in associated drug crimes or youth usage rates after passage of state laws allowing medicinal cannabis

He Concludes his paper

Conclusions

As the legal tide is turning on cannabis as a forbidden drug, experiments are ongoing in the various states (and other countries) as called for in Justice Brandeis’ “laboratories of democracy.” Daunting problems remain for those attempting to seek regulatory approval for smoked or vaporized cannabis as a prescription product, whereas nabiximols, a standardized oromucosal spray has achieved such approval in 27 nations based on its ability to demonstrate biochemical consistency, and safety and efficacy in randomized controlled trials. Pure CBD (Epidiolex) also appears headed for regulatory approval.

In contrast, the recreational market is facing numerous challenges in quality control, and addressing myriad safety concerns associated with newer, more potent preparations and novel delivery techniques. Science may provide suitable data for addressing these issues if commensurate research funding is forthcoming to meet the urgent need.

you can read the entire article here –

Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues

Ethan B. Russo

 

Does Cannabis Use Equal Abuse?

As we have searched through various databases about Cannabis a consistent theme has developed.  Use = Abuse when it comes to Cannabis.

This just doesn’t make any sense.  Just because something is used doesn’t mean it’s abused.  Unfortunately because of state and federal laws, Use = Abuse.  At least that is what it looks like when you look at NIDA and other cannabis studies on use.

It also appears in many law cases.  The accused is said to have a cannabis use disorder.  What is a Cannabis Use Disorder?  Meaning the person violated the state or federal law that Cannabis is a schedule substance and not legal to buy like you can alcohol or tobacco?

Dr. Damon concluded that defendant suffers from … mild cannabis use disorder in a controlled environment, and antisocial personality disorder.

apaAccording to the DSM 5th revision Cannabis Use Disorder is described as

Cannabis use disorder or cannabis dependence is defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as the continued use of cannabis despite clinically significant impairment, ranging from mild to severe.

So Use Disorder, which sounds really bad, is actually not.   “continued use of cannabis despite clinically significant impairment”.  Not DESPITE clinically significant impairment.  So simply using Cannabis is all it takes to get this “Disorder”.  But if there is no impairment how can there be a disorder?  That remains to be understood.

Price of Big Pharm Cannabis

It’s pretty clear with the recent developments that Big Pharm is seriously looking at Cannabinoids.logo  hgDPF-j4_400x400While the vast majority like GW Pharm are using synthetic versions there are plant derived cannabinoids and the plant itself being used in clinical studies.

The cost of Synthetic Cannabinoids is easy to determine.  Sigma-Aldrich offers Cannabinol for $25 a milligram.  A single milligram of THC costs almost $50.  Cannabidiol is also nearly $50 a milligram.  Synthetic Cannabinoid medications are going to be expensive.  Given that a dose of 10mg THC – <1mg CBD needed for pain the cost per dose is going to be over $500.

marijuana-001Plant based medications are in comparison cheap.  Even at the expensive distributors in a very restrictive state like MN you can get 100mg of THC and 4mg of CBD for only $47.00 .  This comes down to $4.70 per effective dose. Clearly plant based extracts of Cannabinoids are cheaper than synthetically produced ones.

Big Pharmacy seems to be interested in making Cannabinoids but will the public be able to afford what they synthetically produce?  Not at $500+ a dose

 

Effects of Vaporized Marijuana

clinicalWhat are the affects of Effects of Vaporized Marijuana?  Are there any adverse events?  How about Serious adverse events? According to a small study done at the University of California, Davis with the collaboration of the Center for Medicinal Cannabis Research, VA Northern California Health Care System, nope.

In a study on Effects of Vaporized Marijuana on Neuropathic Pain they not only found that a significant number of participants benefited with lower pain levels, they also reported No Events of any significance.  The study included what they call low (1.29% THC) and medium (3.53%) and a placebo.

Surprisingly this study has been sitting on ClinicalTrials.gov since it’s completion in 2013

Here is a link to the study – ClinicalTrials.gov NCT01037088