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As a physician specializing in cannabinoid medicine, I am often asked about drug testing.  After over a half of a century of America’s so-called “War on Drugs”, testing for cannabis use has become embedded into our nation’s sense of public safety and liability, becoming commonplace not only in hospitals and criminal investigations, but, even more unfortunately, at many a cannabis user’s workplace.  This is a big, complicated and evolving subject, and yet another example of individual liberties being subverted by fear and ignorance, without valid scientific justification.  Here is a brief review of the subject, with some attention given to how cannabis is metabolized in the body, approaches to testing, and considerations in safely navigating this test crazy landscape.

There are several ways to test for cannabis use, though none of them accurately gauge impairment (the presumed rationale for testing in the first place.)  Since THC is the primary mind-altering, and hence “impairing”, compound present in cannabis products, it follows that THC levels in the body offer a theoretical measure of impairment.  However, unlike blood alcohol levels, which do approximate predictable levels of impairment, no such correlation exists with THC or any of its metabolites, regardless of sample source.  To better understand this, let us examine what happens to THC when cannabis products are used.

Whether smoked or consumed, the body breaks down THC into several metabolites before they are gradually excreted – 2/3 in the feces and 1/3 in the urine. Because cannabinoids and many of their metabolites are fat soluble, chronic use can lead to their accumulation in fatty tissues. Over time these compounds, some with medicinal and psychoactive properties, are released back into the bloodstream and excreted.

When smoked, THC passes directly into the bloodstream and is carried throughout the body and brain.  THC blood concentration peaks quickly within the first ten minutes of smoking, abruptly falls within the first hour and then gradually tails off to undetectable levels at differing rates depending on frequency of use – 12 hours or so after single use and up to a week in chronic users. 

When THC passes through the liver following consumption (and eventually after smoking), much THC is converted into the non-psychoactive metabolite THC-COOH and the psychoactive metabolite 11-OH-Hydroxy-THC  (not appreciably present in blood when cannabis is smoked). Levels of THC and these metabolites slowly rise to detectable levels within the first hour following ingestion, continue to rise and then plateau for 4-6 hours and then slowly tail off to undetectable levels – the rate of taper being dependent on a number of variables – most notably including chronicity of use.  

By far the most common approach to drug testing is urinalysis.  While more sensitive urine drug screens exist, most are designed to detect the liver break-down metabolite THC-COOH, which lingers in the body long after the effects of THC have passed away.  THC-COOH levels remain detectable for days or even weeks after last administration in infrequent users and up to 2 months in chronic users.  There is no correlation between presence of THC-COOH in urine and intoxication.  In fact, the U.S. Dept. of Justice has even admitted, “a positive test, even when confirmed… does not indicate abuse or addiction, recency, frequency, amount of use or impairment.”

Of all tests presently available blood tests most accurately measure the actual presence of THC in the bloodstream.  Because blood tests register positive for just a few hours after use, they provide the best gauge of recent impairment.  Blood THC levels can, however, remain detectable in chronic users for up to 2 days after smoking, so positive tests don’t necessarily reflect impairment.  Most blood drug screens only screen for the presence of THC, but there are exceptions.

Cannabis users who are subject to drug screening have several options.  The most upright approach is to abstain from use long enough to clear its tested metabolites out of the body.  This timeframe ranges from 12 hours to 2 months, and the only way to know for certain is to test oneself beforehand.  Large intake of fluids immediately prior to the test can often dilute one’s urine enough to increase the odds of passing the test.  Water is fluid of choice, and even if the testing lab invalidates the test owing to overdilution of urine, any follow up testing is further removed from last use.  Another successful, if tricky, method used to foil urine tests is to use synthetic or otherwise clean urine, which must be at body temperature (90-98 deg F).  Keep in mind, however, that medical cannabis is still illegal in Carolina, so weigh medicinal benefits against potential legal consequences. 

Some users obtain a Marinol prescription for protection.  Laboratories are legally required to report drug screens as “negative” when informed beforehand that the individual being tested is using a prescription for a medication prone to yield a positive result.  Because Marinol is a synthetic isomer of THC, it is metabolized in the same way as its plant analog.  Unless the laboratory is looking for cannabinoids (or their metabolites) other than THC, a Marinol prescription offers cannabis users even more lab testing safety than the medical cannabis cards available in states with such allowances.  Many physicians are hesitant to prescribe Marinol, especially in a medical cannabis deprived state like North Carolina, because of its association with cannabis.  In states friendly to medical cannabis, it can serve as a useful, albeit inferior, substitute for the herbal form – during airline travel, in smoke-free zones, at one’s workplace and at times when a patient’s medical cannabis supply is depleted.  Cannabis and Marinol are both regarded with a double standard when compared to other medications, but this double standard also weighs in Marinol's favor (when compared to cannabis use), so the argument that cannabis works better for you than other prescription medications may prove useful when trying to convince a physician to prescribe Marinol.

In conclusion, tests aimed at detecting cannabis in the body reflect a severely flawed sense of justice, particularly when livelihoods are on the line.  Reflecting neither ability to work safely nor lack of ability to perform one's job duties, these ignorant violations of privacy cannot always be avoided at the workplace.  Ironically, because cannabis alleviates symptoms that render patients less able to live fully, many are MORE functional after medicating with cannabis.  Until Corporate America gets enlightened on the subject, cannabis users are wise to develop awareness themselves to best prepare for the possiblity of being drug tested.

(Much of this information sourced from the Marijuana Medical Handbook by Gieringer, Rosenthal & Carter, Quick American, 2008. Additional scientific references available by request.)

In last week's post on the Endocannabinoid System I promised to discuss cannabinoids in greater detail.  These are, of course, the movers and shakers of the endocannabinoid (eCB) system – in other words, the compounds which activate eCB receptors, which, in turn, modulate and regulate our nervous and immune systems, and hence help maintain homeostasis (systemic balance) throughout the entire body.  Several categories of compounds are worth mentioning:  endocannabinoids, phytocannabinoids, cannabinoid modulators and synthetic cannabinoids.

The endocannabinoids (eCBs) are synthesized in the body itself.  The two known eCBs are anandamide and 2-AG (2-aracidonylglycerol).  They are produced "on demand" from arachidonic acid in cell membranes and only activate receptors near-at-hand because they are immediately metabolized (broken down).  Because arachidonic acid is a common Omega-6 fatty acid, diet can influence production of eCBs.  Anandamide and 2-AG seem to exert different effects on the eCB system, and whereas 2-AG is a full agonist (fully stimulates eCB receptors), anandamide is only a partial agonist.  This distinction is important because partial agonists tend to cause less desensitization and down regulation of their target receptors (which is to say, less tolerance develops.)

The phytocannabinoids (usually just called cannabinoids) are a group of at least 60 compounds with similar molecular structure found exclusively in the cannabis plant.  Like the eCBs, the different cannabinoids (CBs) also exert varying effects on the eCB system.  The two most prominent and best studied are THC (short for delta-9-tetrahydrocannabinol) and CBD (cannabidiol).  Like anandamide, THC is parital agonist on eCB receptors.  Curiously, researchers have yet to locate the receptors to which CBD binds.

The medicinal effects of cannabis seem to depend primarily on its THC content.  Cannabis treated to remove THC, while preserving other CBs present, has yet to demonstrate significant pharmacological effect.  Alone THC is best known for its psychoactive effects, but it has also anti-emetic, antispasmodic, anti-proliferative (anti-tumoral) and appetite stimulant effects as well, but other CBs (most notably CBD) modulate and add to these effects.

THC & CBD seem to work both in synergy and opposition.  CBD enhances the expression of CB1 receptors in the brain, decreases tolerance to THC, stimulates the release of 2-AG and inhibits the breakdown of anandamide.  While CBD blunts the psychoactive "high" that THC delivers, it also appears to blunt the paranoia that can accompany THC use and counteract the link (extremely weak as it is) between THC use and depression and psychosis in those predisposed to such mental illness.  Even more amazing, CBD appears to magnify THC's inhibitory effect on certain forms of cancer.  CBD also adds analgesic, anti-inflammatory, anticonvulsant, antiarrhythmia, antidiabetic, antibacterial, antioxidant, neuroprotectant, and neurogenic effects.

Cannabinoids 

THC & CBD are actually members of several subclasses of cannabinoids which have been identified.  The THC type includes 9 cannabinoids with similar chemical structure and properties, though delta-9 tetrahydrocannabinol is considered the most psychoactive (whereas its acid precursor is not.)  The CBD type includes 7 cannabinoids with similar structure, cannabidiol being the most prevalent.  The CBG (cannabigerol) type, which includes 5 related compounds, and the CBC (cannabichromene) type, which includes 5, have been shown to have anti-proliferative, anti-inflammatory, analgesic, bone stimulant, antimicrobial effects.  There are also delta-8 THC types, cannabinol types and cannabinodial types.

Also present in the cannabis plant are compounds which, though not cannabinoids by chemical classification, contribute synergistic healing effects and may also modulate cannabinoid activity.  These include terpenoids and flavenoids.  The terpenoids, numbering over 100 in cannabis, but also found in citrus, pine and hops, give each strain its unique smell, and some have shown to have anti-cancer activity.  The flavonoids, widespread throughout the plant kingdom, number around 20 in cannabis, and have been shown to have anti-inflammatory, anti-oxidant and anxiolytic effects.  In addition, terpenoids and flavonoids may increase cerebral blood flow, enhance brain function and kill respiratory pathogens.  Several plants produce compounds that modulate the immune system by selectively binding to CB2 receptors.  For example, alkamides in Echinacea species directly bind to CB2, and alkamides also inhibit the breakdown of anandamide.  And Beta-caryophyllene in black pepper (also in cannabis) binds to CB2, demonstrating anti-inflammatory effects.

Without general awareness, many have been modulating their endocannabinoid system with pharmaceuticals also.  One of metabolites of acetaminophen (tylenol) activates CB1 receptors and inhibits anandamide reuptake and breakdown.  NSAID drugs like ibuprofen inhibit the enzyme which breaks down 2-AG and enhance anandamide activity.  Given the evidence that the eCB system modulates pain, it is probable that such medications alleviate pain in part because of their effect on the eCB system.  Several classes of psychiatric medications increase and/or decrease expression of CB1 receptors in the brain.  No doubt, many more medications will prove to influence the endocannabinoid system, for better or worse.

If one truth can be weaned from this summary so far, it is that the many naturally occurring compounds found in the cannabis plant work synergistically with one another.  This fact challenges the mainstream pharmaceutical model, which generally demands that medicinal compounds be isolated, concentrated, and quantified into specific doses.  I daresay, cannabis does not so much fail this model as federal regulators and allopathic dogmatists tend to argue, but rather it is this pharmaceutical model which fails those doctors and patients who would chose to use cannabis in its natural state simply because it works.  This failure has been exemplified by several attempts to deliver single synthetic cannabinoids.

Synthetic cannabinoids are, of course, man made.  The prime example is dronabinol (called marinol when encapsulated with sesame oil), which is a synthetic isomer of THC.  While it is effective in treating many of the same conditions cannabis treats, research and anecdotal evidence proves it less effective than the herbal form.  Making things worse, while no death has ever been directly associated from cannabis use, a few deaths have been attributed to the dronabinol.  Also of concern are the many emerging synthetic cannabinoids being sprayed on herbs and sold for recreational use under names like “Spice”.  Severe adverse effects (far in excess of any associated with cannabis use) and possibly even a few deaths have been linked to use of these compounds.  One such synthetic cannabinoid, HU-210, acts as a super agonist, producing a greater than maximum response than eCBs are capable of producing.  Here (and elsewhere as any responsible naturopath would note) it becomes obvious that a stronger medicine isn’t necessarily a better medicine.  Exceeding nature is a risky business indeed, particularly in the unregulated world of synthetic recreational drugs.

While the pharmaceutical-industrial complex seems hell-bent on banning the cannabis plant (competition) while patenting synthetic analogs to cannabinoids readily available to every gardener capable of its cultivatation, the nutriceutical industry has offered another option: whole plant extracts.  One such whole plant extract on the market is Sativex, which boasts a 1:1 THC/CBD ratio without the euphoric (so-called) side effect.   Taken sublingually, it is unfortunately not yet available in the United States.  Time will tell how well cannabis based nutriceuticals hold up to the tried and tested approaches of cannabis use.

One thing is sure:  we will be hearing lots more about cannabinoids - especially CBD - in the years to come. Cannabis cultivators the world over are already developing CBD rich strains (4% or greater), and patients are lining up to buy/grow these strains.  In the end, consumer demand, whether in its black market form or in its freer versions is the engine driving medical cannabis research. (Scientific references available upon request.) 

Greetings Carolina!

I have only just returned from Tucson, and there is so much to share. But perhaps I should first introduce myself, as I have been assigned the post of medical director of the North Carolina Cannabis Patient’s Network. I am still uncertain of all the duties this position entails, but I shall do my best at whatever they turn out to be, and I welcome your suggestions.

I’m in a unique position to help the medical cannabis movement in North Carolina. Generally speaking, doctors tend to be very hesitant to involve themselves with the movement, especially when practicing in states that have not yet passed medical cannabis legislation. This is largely out of stigmatic fear of losing their medical licenses, but also out of ignorance. The endocannabinoid system is not taught in medical school, so physicians have to go out of their way to learn about it and how to practically apply this knowledge into patient care. Since I’ve been doing this in the State of Hawaii for over two years now, I’ve learned a lot about the cannabinoid medicine and shed most of my fear concerning its practice. I feel I can speak in Carolina with the confidence of experience that comes from a still thriving out-of-state practice without unduly alarming the N.C. medical board.

For clarity, my wife (Michelle) and I have relocated to Carolina, where we plan to settle, but we continue to return to the Hawaiian Islands on a regular basis to tend our still growing practice (including over 1500 medical cannabis patients.) Despite this rather inconvenient commute, I will do all I can to put my experience in cannabinoid medicine and my N.C. medical license to good use. I am optimistic that Carolina will pass medical cannabis legislation within the next few years, so much so that we already have a company name for our practice to hit the ground running once a medical cannabis law is passed. That company name, “Carolina Compassionate Care” also happens to be the screen name I have using here on NCCPN.org over the last year. As medical director, I thought it appropriate to have a separate screen name for my new position as well.

This last week I was honored to join a delegation from Carolina to the Seventh Clinical Conference on Cannabis Therapeutics hosted by Patients Out of Time in Tucson. Despite all attempts by the federal government to block such research, there is an incredible body of scientifically based information amassing on the endocannabinoid system, and in my next blog posting I shall attempt to share some of this information. But this conference also featured some truly inspiring crusaders in the medical cannabis movement – people who, like many of you, not only have had severe illness to contend with, but a legal system oppressive to those who choose to treat themselves with the safe, natural, non-addictive, effective medicine that is cannabis.

This safety and efficacy of cannabis speaks for itself, so much so that I have tended to shrug off the call to become a professor of cannabinoid medicine. As if I don’t have enough to think about! And yet… such titles inspire some, and so I decided to join a very new organization called the American Academy of Cannabinoid Medicine, and this weekend in Tucson I sat in on their very first examination to become board certified in cannabinoid medicine. (And with any luck I passed the test! I’ll let you know.)

For now, I am honored to serve as medical director to the North Carolina Cannabis Patients Network. I hope to meet you all in meetings throughout the state. Nationwide popular approval of medical cannabis is at an all time high (pun intended!) Together we can bring safe access of medical cannabis to Carolina.

I’m back to share some of the scientific findings presented at the Seventh Clinical Conference on Cannabis Therapeutics hosted by Patients Out of Time in Tucson.  This information is complex, but I’ll attempt to convey it over a series of posts in simple enough terms to be understood by those less scientifically minded.  If it's over your head, remember that cannabis was an effective medicine long before we had any idea as to why, and the top researchers in this field are only just breaking through the surface of the matter, so please don't sweat it.  This stuff isn’t even taught in the majority of, if any, medical schools yet.  Please feel free to ask any questions that come up, so when opportunity arises, you can teach YOUR doctors.

Tongue out

We start with the endocannabinoid (pronounced “en-doe-can-NAB-i-noid”) system.  It was discovered in the early 1990’s that the human body has receptors that respond to a set of at least 60 compounds found in the cannabis plant – called cannabinoids.  (We actually positively respond to other compounds in the plant too – terpenoids & flavenoids - more on all these compounds in another post.)  THC (short for delta-9-tetrahydrocannabinol) is the best known of these cannabinoids – mostly for its psychoactive, but also medicinal effects.  But there are others similar in structure with differing, modulating and probably even more profound healing effects, including CBD (cannabidiol), CBG (cannabigerol), CBC (cannabichromene), to name a few.  It was later discovered that our bodies manufacture compounds that bind to these receptors.  These are called endocannabinoids (eCBs), and at least 2 of them, named anandamide, 2AG (2-aracidonylglycerol) are found in the human body.  It turns out that all chordates (including all animals with a spine) have cannabinoid (CB) receptors, and even more animals synthesize anandamide for some purpose, leading scientists to estimate that CB receptors evolved over 600 million years ago and anandamide even further back.  Considering that the cannabis plant first shows in the fossil record around 25 million years ago, it’s likely that the plant evolved its peculiar set of phytocannabinoids to its own survival advantage in a world full of animals that respond to them.  Regardless, cannabis plant or no, our bodies have CB receptors and create the eCBs that trigger these receptors, which leads us to an obvious line of questioning... What happens when eCB binds to CB receptor?  And even bigger in scope... What does the endocannabinoid system do?

Cool

To better address these questions, we should explore where these receptors – CB1 & CB2 (the two most studied) - are found.  CB1 receptors are primarily found throughout the nervous system, while CB2 receptors are primarily found throughout the immune system.  These two systems are central to adaptation and survival, and arguably regulate and influence every other system in the body.  The endocannabinoid system appears to play a key role in modulating these two systems, serving as a pro-homeostatic (maintaining balance) system for stress recovery and adaptation, facilitating our ability to relax, eat, rest, forget and protect ourselves (Di Marzo et al).  Keep this in mind when people scoff at the capacity of the cannabis plant to treat so many different disease complaints and states of illness.  The endocannabinoid system literally exerts effect, directly or indirectly, on every other system of the body.  That this rudimentary system has been preserved throughout much of the animal kingdom means that animal models work well to predict effects on humans, when our human overlords actually allow such research to take place.

Frown

We can start to appreciate how the endocannabinoid system is so special when we look at how eCBs modulate the nervous system.  Nerves transmit signals throughout the body, and like individual lanes in a highway, individual nerves only transmit signals in a specific direction.  (Like from brain to hand or from toe to spinal cord.) When a nerve releases its neurotransmitter (NT) into the synapse (space between it and the next nerves down the highway lane) NT binds to receptors on the other nerves and trigger a response on the post-synaptic nerve.  Imagine the pre-synaptic nerve as the pitcher and the post-synaptic nerve as the catcher.  The baseball is the neurotransmitter, and it only travels from pre-synapse (pitcher) to post-synapse (catcher) because the pre-synaptic nerve lacks the appropriate receptors on its side of the synapse.  But counter to this model, eCBs are released and received in the opposite direction.  Post-synaptic nerves release an eCB when they been sufficiently stimulated, and the eCBs cross the synaptic space, binding to CB1 receptors on the pre-synaptic nerve, signaling it to stop releasing its NT.  This picture depicts this process... The red dots are the neurotransmitters being released at the endplate of one nerve, diffusing across the synaptic cleft and attaching to their receptor on the next nerve downline.  When this second nerve has had enough of the NT, it releases some eCB (green dots) from its cell membrane, they diffuse across the cell in retrograde direction, attach to the CB1 receptor on the first nerve, signaling it to stop the NT release...

                                  cb signaling in synapse

In other words, eCBs provide a direct negative feedback in nerve signalling, keeping its cellular stress in check at the synaptic level.  That eCBs are the only known neurotransmitters to perform this retrograde neuroregulation suggests their primary role in keeping the nervous system – and therefore all other systems – in a healthy balance (homeostasis).

Surprised

Considering the direct effects of endocannabinoids on both the nervous system - especially the brain centers thought to most influence emotional processing (amygdaloid nucleus, hippocampus & prefrontal cortex) and the immune system (including white blood cells and glands like the adrenal), it follows that eCBs directly influence emotional health.  In fact, there is an inverse relationship between 2-AG levels in the hypothalamus and blood levels of cortisol (stress hormone released by adrenal gland).  In other words, eCBs help us deal with small spurts of emotional stress, wheras chronic emotional stress inhibits our ability to maintain emotional balance – leading to a spectrum of unpleasant and even pathological emotional states.  This inverse relationship works both ways, as demonstrated when an emotionally stressed individual uses some cannabis and homeostasis is restored.

Smile

Dysregulation of the endocannabinoid system is being linked to a growing list of medical conditions.  When the endocannabinoid system’s plasticity (ability to normalize cellular stress) is compromised a chain reaction of neuro-inflammation, excitotoxicity (under regulated nerves) and production of free radicals begins, leading researchers to believe that over time abnormal plasticity causes disease in organs and organ systems.  Too little plasticity has been linked to epilepsy, Alzheimer’s dementia, depression and certain forms of cancer.  Too much plasticity in the wrong cell or at the wrong time has been linked with obesity and ensuing metabolic disorders (diabetes & dyslipidemia), propensity to addictions, and Parkinson’s disease.  Too much plasticity at the wrong receptor has been linked to osteoporosis, atherogenic inflammation and atherosclerosis.  Even from only these primary findings we get the point... A properly working endocannabinoid system in crucial to health.  Cannabis supplementation in itself probably goes a long way in helping this system to keep our many body’s cells & systems healthfully working in concert with one another, but there is obviously much more going on in the many ways the endocannabinoid system can go out of whack, which begs for more research on this subject.

Money mouth

One area of research which scientists, cannabis cultivators and patients are only just beginning to explore is the effect of many cannabinoids themselves.  Not only do the cannabinoids effect the body in different ways, but different ratios of these cannabinoids effect the body in different ways.  But this discussion is best left to another post.  Stay tuned. 

Wink 

(Scientific references available upon request.) 

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