Cannabidiol is still, yes still, a Schedule I drug. Epidiolex notwithstanding

Yes, the DEA still continues to keep cannabidiol (CBD) on the list of Schedule I drugs. I took this up in December of 2016 and the issues continue.

The new-ish bit, I suppose, is that the FDA approved GW Pharma’s cannabidiol product Epidiolex for Dravet Syndrome and Lennox-Gastaut Syndrome, which involve uncontrollable seizures. This all flows from the “Charlotte’s Web” phenomenon, which was desperate parents seeking help from a specific CBD-dominant strain of cannabis.

This meant that the DEA had to reschedule CBD as a compound with medical application. The reporting from CNBC says Schedule V:

Epidiolex will be classified as a schedule 5 controlled substance, the lowest level, defined as those with a proven medical use and low potential for abuse. Other drugs in this category include some cough medicines containing codeine.

But. However. Not so fast. Apparently the DEA has decided to re-schedule CBD ONLY in the context of FDA approved products. From the same report:

The rescheduling applies to CBD containing no more than 0.1 percent THC, in FDA-approved drug products. Though this allows GW Pharma to sell Epidiolex, it does not broadly apply to CBD.

emphasis added.

This is getting increasingly ridiculous. It is really, really, really clear that CBD does not have the fun recreational drug properties of good old delta-9-tetrahydrocannabinol. It is hard to find much effect of this compound at all*, despite all the quack remedy type products that are illegally on sale in the country at the moment.

I don’t understand how CBD got on the Schedule I list in the first place, nor why the DEA didn’t take this convenient opportunity to re-schedule it altogether.

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*The anti-seizure properties seem solid.

N.b., As per my usual disclaimer, I may have held, hold, or be seeking to hold research funding involving CBD. Please read my comments with that in mind.

Cannabidiol is still Schedule I, where it has been for some time

The DEA has created a new drug
Code for cannabis extracts, leading to some feather fluffing in the advocacy press.

The Federal Register notice explaining this is pretty clear so I’m not seeing where the alleged confusion lies.

The part responding to prior comment makes the situation with cannabidiol (CBD) very explicit.

One comment requested clarification of whether the new drug code will be applicable to cannabidiol (CBD), if it is not combined with cannabinols.

DEA response: For practical purposes, all extracts that contain CBD will also contain at least small amounts of other cannabinoids.1 However, if it were possible to produce from the cannabis plant an extract that contained only CBD and no other cannabinoids, such an extract would fall within the new drug code 7350. In view of this comment, the regulatory text accompanying new drug code 7350 has been modified slightly to make clear that it includes cannabis extracts that contain only one cannabinoid.

CBD has been on the Schedule for quite some time as far as I know. It is listed specifically on the application for a researcher license. You won’t be able to buy it from a legitimate scientific reagent company such as Sigma without a DEA license. Very hard to miss.

I am aware of some very dodgy stuff going on with CBD for the quack supplement industry. From what I can tell, some of these companies are importing pure CBD under cover of “industrial hemp”. Hemp is defined by lack of delta9-THC content, of course. Making “hemp” that contains high levels of the clearly Scheduled CBD a very gray area. It will be interesting to see if part of the outcome of this new extracts code will be invigorated prosecution of these CBD supplement companies.

Cannabis hyperemesis syndrome rates increase with marijuana legalization

A report by CBS News reports on a 2015 paper:

Howard S. Kim, MD, John D. Anderson, MD, Omeed Saghafi, MD, Kennon J. Heard, MD, PhD, and Andrew A. Monte, MD Cyclic Vomiting Presentations Following Marijuana Liberalization in Colorado. Acad Emerg Med. 2015 Jun; 22(6): 694–699.
Published online 2015 Apr 22.
[pubmed

From the Abstract:

The authors reviewed 2,574 visits and identified 36 patients diagnosed with cyclic vomiting over 128 visits. The prevalence of cyclic vomiting visits increased from 41 per 113,262 ED visits to 87 per 125,095 ED visits after marijuana liberalization, corresponding to a prevalence ratio of 1.92 (95% confidence interval [CI] = 1.33 to 2.79). Patients with cyclic vomiting in the postliberalization period were more likely to have marijuana use documented than patients in the preliberalization period (odds ratio = 3.59, 95% CI = 1.44 to 9.00).

For background on the slow, Case Report driven appreciation that a chronic cyclical vomiting syndrome can be caused by cannabis use, see blog posts here, here, here.

The major takeaway message is that when physicians or patients are simply aware that there is this syndrome, diagnosis can be more rapid and a lot less expensive. Patients can, if they are able to stop smoking pot, find relief more quickly.

As far as the present report showing increasing rates in CO, well, this is interesting. Consistent with a specific causal relationship of cannabis use to this hyperemesis syndrome. But hard to disentangle growing awareness of the syndrome from growing incidence of it. We’ll just have to follow these relationships as more states legalize medical and recreational marijuana.

Additional coverage from Dirk Hansen.

NPR on trying to create DUI regulation for marijuana

NPR had a good segment on this today: The Difficulty Of Enforcing Laws Against Driving While High. Definitely well worth a listen.

I had a few reactions in a comment that ended up being post-length, so here you go.

The major discussion of the segment was two-fold and I think illustrates where policy based on the science can be helpful, even if only to point to what we need to know but do not at present.

The first point was that THC hangs around in the body for a very long time post-consumption, particularly in comparison with alcohol. Someone who is a long term chronic user can have blood THC levels that are…appreciable (no matter the particular threshold for presumed impairment, this is relevant). Some of the best data on this are from the laboratory of Marilyn Huestis when she was, gasp, an intramural investigator at NIDA! There are some attempts in the Huestis work to compare THC and metabolite ratios to determine recency of consumption-that’s a good direction. IMO.

The second argument was about behavioral tolerance. One of the scientist interviewed was quoted along the lines of saying the relationship between blood levels, repetitive use and actual impairment was more linear for alcohol than for THC. Pretty much. There is some evidence for substantial behavioral tolerance, meaning even when acutely intoxicated, the chronic user may have relatively preserved performance versus the noob. There’s a laboratory study here that makes the point fairly succinctly, even if the behavior itself isn’t that complex. As a counterpoint, this recent human study fails to confirm behavioral tolerance in an acute dosing study (see Fig 4A for baseline THC by frequency of use, btw). As that NPR piece noted, it would be very valuable to get some rapid field screen for THC/driving – relevant impairment on a tablet.

Pot Ponder

Five states have recreational marijuana legalization on the ballot this fall, if I heard correctly. 

I feel as though we should probably talk about this over the next couple of months. 

ETA:
Arizona

California

Maine

Massachusetts

Nevada

As most of you are aware, these follow successful recreational legalization initiatives in Washington (2012), Colorado (2012), Oregon (2014), Alaska (2014) and the District of Columbia (2014).

CPDD 2016: Thought of the Day

There is a lot of focus on cannabis this year. Much more than usual, seemingly.

And everyone talks about how it is the growing legalization (medical and recreational) that is the driving justification.

I find this to be interesting.

That may not be nicotine that those kids are vaping with that e-cigarette

By now most of you are familiar with the huge plume of vapor emitted by a user of an e-cigarette device on the streets. Maybe you walked through it and worried briefly about your second-hand vape exposure risk. Some of you may even have been amused to hear your fellow parents tell you with a straight face that their kids “only vape the vehicle for the flavor”. Sure. Ahem.

Nicotine is one thing, but there is also a growing trend to use e-cigarettes to vape marijuana and, allegedly, stimulants such as flakka (alpha-PVP).

As with many emerging drug trends it can be difficult to put solid, peer-reviewed epidemiology on the table to verify these behaviors.

A recent paper reports on some initial estimates on practices among middle- and high-school students.

High School Students’ Use of Electronic Cigarettes to Vaporize Cannabis. Morean ME, Kong G, Camenga DR, Cavallo DA, Krishnan-Sarin S. Pediatrics. 2015 Oct;136(4):611-6. doi: 10.1542/peds.2015-1727. Epub 2015 Sep 7.[PubMed]

The authors surveyed 5 High Schools and 2 middle schools in Connecticut in the spring of 2014. Apparently insufficient middle school data were obtained so the paper focuses on the high school respondents only.

There were three key questions for the purposes of assessing behavior rates. Students were classified as “never used” or “lifetime used” (for ever having tried at least once) for e-cigarette use, for cannabis use (any method) and for cannabis use with an e-cigarette device.

Out of the total sample of 3847 HS students who completed the entire survey (52% female), about 5.4% had used an e-cigarette to self-administer cannabis. If, however, the sample was limited to those who had ever used an e-cigarette, then 18% had used one to administer cannabis. For lifetime cannabis users, it went to 18.4% and for dual e-cigarette and cannabis users, 26.5%.

So while the majority of high school students who have ever tried cannabis have never tried using an e-cigarette to dose themselves, 20% is a sizeable minority.

As always, it will be most interesting to see where these trends go and how they extend to older user groups. It could be that it is something that kids try and abandon (perhaps due to not learning different inhalation topography necessary for the desired high as with nicotine). It may be that older users are loathe to change their established patterns or see no advantages to e-cigarettes. I anticipate that solid data on these trends will be slow to emerge but I’ll be keeping an eye out.

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Relatedly, the research community has been responding to this trend, and I wanted to draw two new papers to your attention.

Marusich and colleagues report from the Wiley group at RTI that they have a new model of flakka (and methamphetamine) delivery that increases locomotor activity and induces place preference in mice.

Pharmacological Effects of Methamphetamine and Alpha-PVP Vapor and Injection, Julie A. Marusich, , Timothy W. Lefever, Bruce E. Blough, Brian F. Thomas, Jenny L. Wiley, 2016, Neurotoxicology, doi:10.1016/j.neuro.2016.05.015

Nguyen and colleagues report from the Taffe group at TSRI that they have a new model of THC delivery that induces hypothermia, hypolocomotion and anti-nociception in rats.

Inhaled delivery of Δ9-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology, Jacques D. Nguyen, Shawn M. Aarde, Sophia A. Vandewater, Yanabel Grant, David G. Stouffer, Loren H. Parsons, Maury Cole, Michael A. Taffe, 2016, Neuropharmacology,doi:10.1016/j.neuropharm.2016.05.021

Marijuana Use, Abuse and Dependence Increased Over the Past Decade

A new paper from Hasin and colleagues at JAMA Psychiatry reviews data:

from NESARC and from the National Institute on Alcohol Abuse and Alcoholism
2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions–III (NESARC-III), a survey of 36,309 new participants.
…
The NESARC field procedureswere similar to those in NESARC-III.

There are really three key observations, although the tables also break down the findings by sex, age, race/ethnicity, education level, etc.

First, past year use of marijuana went from 4.1% to 9.5% of the sampled populations. Interesting, but hey, could just be more people feeling free to try it out, right?

Second finding looked at prevalence of meeting DSM-IV criteria for a Marijuana Use Disorder (including Abuse and Dependence subcategories) in the past year. This measure went from 1.5% to 2.9% of the population.

The third finding is that if you condition only upon those individuals who have tried marijuana at least once in the past year, the rate of a Marijuana Use Disorder went from 35.6% to 30.6%.

This is all relevant to a few themes we’ve discussed before on the blog.

I don’t see how you can view these data other than in a context of growing liberalization of medical marijuana laws and availability of marijuana. This refutes the occasional position struck by the pot fans that changes in legal status and attitude won’t change use rates because everyone who wants to smoke marijuana already does. Clearly the US population undergoes significant changes in exposure to marijuana. In this case only over a decade.

My position has also been that, in general, as you increase the number of people who are exposed to a given drug you are going to see an increase in problems related to that drug. In the absence of other information, we must start our estimate of that rate from what we observe at a given time. The first two numbers in the study confirm this. As use rates increased, so did rates of meeting criteria for DSM-IV diagnosis of a MUD.

The conditional probability measure also addresses this phenomenon, perhaps in an even better way. I have mentioned before that it is really hard to assess conditional probability of dependence between drugs that feature significant base-rate exposure differences. You can’t help but assume there is going to be a curve whereby the more democratic the exposure, the larger will be the occasional user population. That is, I assume some sort of nonlinearity is going to occur against the general estimation I mention above. I presume the lower the incidence of exposure to a given drug, perhaps the higher the conditional probability of dependence and the higher the incidence of exposure, the lower the conditional probability.

In this case, I’d say the change in conditional probability is not that significant. Something around a third of those who smoke marijuana in a given year are meeting criteria for a MUD across a doubling of the incidence of exposure. The curve is still pretty linear although I assume we will be getting another jump in a decade and can see how this curve shapes up.

This estimate of a MUD is really high to my eye, no doubt because it includes abuse and dependence together. Perhaps the data I usually think about (7-9% dependence rate) references dependence without abuse…I have to go check on that. In case you are wondering, the difference really boils down to symptoms of tolerance (diminished effect at same dose, increasing dose to get desired effect) and withdrawal, as well as some indicators of uncontrolled use relative to a person’s intentions.

Now interestingly the authors reference another similar study (NSDUH) that didn’t find an increase in prevalence that was so large- only 12% reported by Pacek et al, 2015. The present authors suggest more detailed questioning in the NESARC approach may explain the difference.

The Daily Show is just plain wrong on pot being non-addictive

In the 420 bit from this week, Jessica Williams asserts that marijuana is “a non-addictive proven medical treatment“.

Marijuana is most certainly addictive.

In 2012, 17.5% of all substance abuse treatment admissions had marijuana as their primary abused drug. Alcohol alone was 21.5%, heroin 16.3% and cocaine 6.9%.

Daily marijuana smokers use 3 times a day on average and have little variability from day to day.

Pregnant women are unwilling or unable to stop smoking pot almost daily. Increasing numbers of pregnant women are seeking help to discontinue pot use.

At least one woman found out her hyperemesis during pregnancy was the pot, not morning sickness.

Marijuana is addictive in adolescents.

When adolescents stop smoking weed, their memory gets better.

About six percent of High School seniors are smoking pot almost every day.

Clinical trials of medications to help people who are addicted to marijuana stop using are far from rare.

Francophones are addicted to pot.

Yes, Dutch people are addicted to pot.

Many Cases of cannabis hyperemesis syndrome are unable to stop smoking pot, even though it is severely incapacitating them.

Marijuana is addictive.

About 37% of frequent pot users will transition to dependence in three years.

Oh, and pot users are not awesome, friendly and mellow, actually nondependent users are impulsive and hostile on the day they use pot compared with nonsmoking days.

420andme

I just had this genius idea.

A public science service modeled on 23andme where you send in your pot sample for both genetic analysis (“You have new strain-relatives, want to connect and share experiences?”) and content of various cannabinoids and what not. Add in some health survey stuff and away we go.

Health report from Colorado: Recreational marijuana harms

a Reader put me onto a new Viewpoint in JAMA:

Monte AA, Zane RD, Heard KJ. The Implications of Marijuana Legalization in Colorado.JAMA. 2014 Dec 8. doi: 10.1001/jama.2014.17057. [Epub ahead of print][JAMA; PubMed]

The authors are from the Department of Emergency Medicine, University of Colorado and the Rocky Mountain Poison and Drug Center. They set out to describe a few health stats from before and after the recreational legalization of marijuana.

Interesting tidbits:

However, there has been an increase in visits for pure marijuana intoxication. These were previously a rare occurrence, but even this increase is difficult to quantify. Patients may present to emergency departments (EDs) with anxiety, panic attacks, public intoxication, vomiting, or other nonspecific symptoms precipitated by marijuana use. The University of Colorado ED sees approximately 2000 patients per week; each week, an estimated 1 to 2 patients present solely for marijuana intoxication and another 10 to 15 for marijuana-associated illnesses.

This one is obviously frustratingly anecdotal in that there is no real measure of the rate before legalization.

The one on cyclic vomiting syndrome is better:

The frequent use of high THC concentration products can lead to a cyclic vomiting syndrome. Patients present with severe abdominal pain, vomiting, and diaphoresis; they often report relief with hot showers. A small study at 2 Denver-area hospitals revealed an increase in cyclic vomiting presentations from 41 per 113 262 ED visits to 87 per 125 095 ED visits (prevalence ratio, 1.92) after medical marijuana liberalization (A. A. Monte, MD, unpublished data, December 2014).

We’ve discussed the phenomenon of cannabis hyperemesis before on the blog. One thing we do have to be careful about is that since it has only been recently that the medical community has been alerted to the possibility of cannabis hyperemesis, we should expect the detection rate to increase. Thus, even against a stable rate of cannabis hyperemesis I would expect the reported rate to be increasing.

The University of Colorado burn center has experienced a substantial increase in the number of marijuana-related burns. In the past 2 years, the burn center has had 31 admissions for marijuana-related burns; some cases involve more than 70% of body surface area and 21 required skin grafting. The majority of these were flash burns that occurred during THC extraction from marijuana plants using butane as a solvent.

This is the e-cigarette and vape market at work people. In South Florida they apparently call it ‘Budda’.

Apparently some basic pharmacology 101 would be of help to the good citizens of Colorado.

Edible products are responsible for the majority of health care visits due to marijuana intoxication for all ages. This is likely due to failure of adult users to appreciate the delayed effects of ingestion compared with inhalation. Prolonged absorption complicates dosing, manufacturing inconsistencies lead to dose variability

Interesting. I recall the language in the original initiative was very vague about product testing, labeling, etc. Looks like this is a problem.

Ten to 30 mg of THC is recommended for intoxication depending on the experience of the user; each package, whether it is a single cookie or a package of gummy bears, theoretically contains 100 mg of THC. Because many find it difficult to eat a tenth of a cookie, unintentional overdosing is common. Furthermore, manufacturing practices for marijuana edible products are not standardized. This results in edible products with inconsistent THC concentrations, further complicating dosing for users. According to a report in the Denver Post, products described as containing 100 mg of THC actually contained from 0 to 146 mg of THC.8

Oh, and the children. Don’t forget about the children.

The most concerning health effects have been among children. The number of children evaluated in the ED for unintentional marijuana ingestion at the Children’s Hospital of Colorado increased from 0 in the 5 years preceding liberalization to 14 in the 2 years after medical liberalization.3 This number has increased further since legalization; as of September 2014, 14 children had been admitted to the hospital this year, and 7 of these were admitted to the intensive care unit. The vast majority of intensive care admissions were related to ingestion of edible THC products.

This Viewpoint certainly draws attention to the edibles/consumables products as being a problem. Seems pretty clear that maturation of product regulation would be a start, so that people are informed about what they are getting. This should probably be supplemented with some sort of public information campaign on the pharmacokinetics of ingested products compared with smoking marijuana. And, you know, keep it away from your kids.

Leegalizeetmon

Looks like both Oregon and Alaska passed initiatives to legalize the recreational use of marijuana.

Interesting.

UPDATE:
Oregon’s initiative.

Alaska’s initiative.

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Oregon:

(1) A person commits the offense of use of marijuana while driving if the person uses any marijuana while driving a motor vehicle upon a highway.

(2) The offense described in this section, use of marijuana while driving, is a Class B traffic violation.

a related item that I like because it calls for research:

(4) On or before January 1, 2017, the commission shall:

(a)Examine available research, and may conduct or commission new research, to investigate the influence of marijuana on the ability of a person to drive a vehicle and on the concentration of delta-9 tetrahydrocannabinol in a person’s blood, in each case taking into account all relevant factors; and
(b) Present the results of the research to the Legislative Assembly and make recommendations to the Legislative Assembly regarding whether any amendments to the Oregon Vehicle Code are appropriate.

weird exception:

(13) “Marijuana extract” means a product obtained by separating resins from marijuana by solvent extraction, using solvents other than vegetable glycerin, such as butane, hexane, isopropyl alcohol, ethanol, and carbon dioxide.

aha, found this part:

SECTION 57. Homemade marijuana extracts prohibited. No person may produce, process, keep, or store homemade marijuana extracts.

so you can’t make solvent extractions for home use but you *can* make vegetable glycerine extractions. Weirder. If the idea is to keep people from doing dangerous stuff with explosive solvents, this would be solved short of prohibiting “keep, or store homemade marijuana extracts”, no?

In case you are wondering, vegetable glycerine extracts can be used in vape pen / e-cig type devices.

Alaska:

(b) Nothing in this chapter is intended to allow driving under the influence of marijuana or to supersede laws related to driving under the influence of marijuana.

Szalavitz on marijuana addiction

If I’m going to bash a journalist when she writes something horrible about drug abuse, I must take pains to congratulate her when she writes something pretty good.

Maia Szalavitz’ latest “Of course Marijuana addiction exists and it’s (almost) all in your head” is actually not bad.

Repost: The War on Drugs Didn't Work, Eh?

There’s a strawman-tilting screed up over at substance.com from my current favorite anti-drug-war-warrior Maia Szalavitz. She’s trying to assert that Trying to Scare Teens Away From Drugs Doesn’t Work.

In this she cites a few outcome studies of interventions that last over relatively short periods of time and address relatively small populations. I think the most truthful thing in her article is probably contained in this quote:

Another study, which used more reliable state data from the CDC’s Youth Risk Behavior Survey, concluded that “When accounting for a preexisting downward trend in meth use, effects [of the Montana Meth Project] on meth use are statistically indistinguishable from zero.”

This points out the difficulty in determining broad, population based outcomes from either personal introspection (where a lot of the suspicion about anti-drug messaging comes from, let’s face it) or rather limited interventions. Our public policy goals are broad- we want to affect entire national populations…or at least state populations. In my view, we need to examine when broad national popular behavior shifted, if it did, if we want to understand how to affect it in the future.

The following originally appeared 21 July 2008.

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If you are a reader of my posts on drug abuse science you will have noticed that it rarely takes long for a commenter or three to opine some version of “The (US) War on Drugs is a complete and utter failure”. Similarly, while Big Eddie mostly comments on the liberty aspects (rather than the effectiveness) of the WoD himself, a commenter to his posts will usually weigh in, commenting to a similar effect.

Now I’m open to all the arguments about personal liberty trade offs, economic costs, sentencing disparities, violations of other sovereign nations and the like. Nevertheless, I’m most interested in the fundamental question of whether the War on Drugs worked. That is, to reduce drug use in the US. For those who believe it has not worked, I have a few figures I would like explained to me.

Medical marijuana "researcher" fired by U of A

From the LA Times:

The University of Arizona has abruptly fired a prominent marijuana researcher who only months ago received rare approval from federal drug officials to study the effects of pot on patients suffering from post traumatic stress disorder.

The firing of Suzanne A. Sisley, a clinical assistant professor of psychiatry, puts her research in jeopardy and has sparked indignation from medical marijuana advocates.

I bet. Interestingly I see no evidence on PubMed that this Sisley person has any expertise in conducting research at all. I’m not saying I need exhaustive credentials but I’d like to see a published study or two.

Cue the usual raving about how this is all a vast right wing conspiracy to keep down miraculous medication…

Sisley charges she was fired after her research – and her personal political crusading – created unwanted attention for the university from legislative Republicans who control its purse strings.

“This is a clear political retaliation for the advocacy and education I have been providing the public and lawmakers,” Sisley said. “I pulled all my evaluations and this is not about my job performance.”

Well, this IS Arizona we’re talking about. I’m going to want to see more* but I guess I am going to have to score myself as sympathetic to the notion that this was a political squelching.
Still, the University is denying the charge…

University officials declined to explain why Sisley’s contract was not renewed, but objected to her characterization.

“The university has received no political pressure to terminate any employee,” said Chris Sigurdson, a university spokesman. He said the university embraces research of medical marijuana, noting that it supported a legislative measure in 2013 permitting such studies to be done on state campuses.

Ok, “embraces”, eh? We’ll see if that turns out to be true.

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h/t: clbs

*if this holds true to form the University will be compelled to make a case for how she wasn’t competent at the “clinical assistant professor” category of association with U of A.