The Blood Plasma Concentration Profile

The blood plasma concentration profile (Figure 1) is a simple, yet rich graphic tool used to communicate either one of three important pieces of information. First, how different drugs affect the human body. Second, how different amounts, or concentrations, of the same drug affect the human body. And third, and most relevant to our discussion, how the same drug affects the human body using different routes of administration.


The blood plasma concentration profile graphically expresses the level of drug in the blood plasma as a function of time. As can be seen in the generic example above, the concentration of the drug in the blood is represented on the y-axis, while time is expressed on the x-axis. The graph starts at t=0 when the drug is administered – for example once the person swallows the pill, lights the joint, or places the patch on their skin.

An important concept indicated in the figure above is the Therapeutic Range. The Therapeutic Range is the difference between MTC and MEC. MTC, the maximum value, stands for Maximum Therapeutic Concentration. It is above this level where a phenomenon akin to the “The Law of Diminishing Returns” takes effect – the actual therapeutic effect may be constant or decreasing, while there is a sharp increase in the side effects. The MEC, the minimum value, stands for Minimum Effective Concentration – the lowest amount of drug that will cause some measurable therapeutic effect. Think of the Therapeutic Range as the sweet spot, that level of the drug in the blood that will maximize the therapeutic effect, while minimizing the side effects.

Chronic pain is, as the name implies, chronic – sufferers typically relate to it as a persistent background noise of pain. Thus the ideal blood plasma concentration profile of cannabinoids that would most optimally address chronic pain would be one that, once it has entered the Therapeutic Range, stays within its bounds for the longest possible duration.

So what is the Minimum Effective Concentration for chronic pain? This is a difficult question to answer as there are many different types of chronic pain with a wide variety of underlying physiological causes. Additionally, we know that individuals respond differently to various medications and dosages. Yet all currently available research on the matter hints that most individuals receive physiological relief from chronic pain symptoms with sub-psychoactive amounts of cannabis. In other words, one can get relief from chronic pain with an amount of cannabis that will not make you high.

The ideal blood plasma concentration profile should supply modest amounts of cannabinoids, consistently, and for the longest possible duration. It should provide maximum relief from chronic pain symptoms, while not making the person high, and thus empower the individual to continue leading a normal and productive life, free from both symptoms of chronic pain as well as cannabinoid-induced inebriation.

We will now explore the blood plasma concentration profiles of the two most common routes of administration for cannabis, pulmonary and oral, and compare it to that of transdermal application. This comparison, in conjunction with the hitherto articulated concepts, will make it clear why transdermal application of cannabinoids is a superior route of administration for a condition such as chronic pain.

Pulmonary Administration

The two most common forms of pulmonary application are smoking and vaping. One either combusts, or vaporizes, the source material – for example cannabis flowers, hashish, shatter etc. This produces a gaseous product which is inhaled, allowing it to cross the lung’s membrane-lining to be absorbed directly into the bloodstream.

Smoking of any kind is harmful to the respiratory system – human lungs evolved to process air and it’s constituents, not combusted organic matter. Though vaporizing clean source material is a less harmful way to consume cannabis via the pulmonary route, the real issue with this route of administration is that its blood plasma concentration profile is non-ideal for a persistent condition such as chronic pain – see Figure 2.


Smoking mimics intravenous administration. You get an immediate spike in blood plasma concentration, which rapidly maxes out and drops sharply as the body metabolizes the compounds.

If one studies the blood plasma concentration profile of pulmonary administration with regards to the Therapeutic Range, one may observe that it rapidly enters and exceeds the range, and then as abruptly crashes below it. The actual time spent in the Therapeutic Range, where the person does not feel mentally affected by the cannabis while experiencing a noteworthy reduction in pain symptoms, is minimal. Smoking cannabis is known as an effective method for getting a person high in a minimum amount of time – hence its popularity for recreational users.

Oral Administration

The second most popular route of administration for cannabis is oral. The medicinal compounds from cannabis, called cannabinoids, are fatty molecules and may be dissolved by using another oily substance, or a solvent such as ethanol. The end product is a highly concentrated form of the drug, which may either be consumed as is, usually dispensed in capsules, or infused within any common foodstuff – from lollipops to hot-sauce.

The blood plasma concentration profile obtained via the oral route (Figure 3) better matches one that ideally treats chronic pain symptoms, provided one does not self-administer an excessive amount. However, the oral route provides a number of challenges to a medical user.


It has a slow and erratic onset, and both inter- and intrapatient variability is notoriously pronounced. The same person using the same dose may experience the effect to be barely noticeable one day, and barely tolerable the next. But the biggest issue with this route is related to an unique pharmacokinetic phenomenon exclusively related to oral administration.

Whenever once consumes a drug via the oral route it is primarily absorbed across the GI tract. Due to the physiological configuration of the human body, when the drug crosses the cells lining the GI tract it enters the blood in a part of the circulatory system called the hepatic portal vein. The blood in the hepatic portal vein then immediately passes through the liver, where most of the compounds are converted into the primary metabolite in a process called first pass metabolism.

In the case of cannabis, the major cannabinoid delta-9-THC, is converted into 11-hydroxy-THC. Thus, as opposed to all other routes of delivery, when one consumes cannabis via the oral route, the main molecule that binds to the receptors is not delta-9-THC, but 11-OH-THC. The reason this is an issue is because 11-OH-THC is thought to be five times more psychoactive than delta-9-THC, without bequeathing any additional therapeutic benefit.

Any experienced cannabis user can testify to this fact – when one eats cannabis the resulting psychoactive effect is much more pronounced. Because one cannot self-titrate in real-time as with smoking, overdosing is a real concern. Though not dangerous (nobody has ever died in the history of mankind due to an overdose of cannabis), when one consumes too much cannabis the experience is typically unpleasant – one may be physically and psychologically debilitated for many hours.

It is for these reasons that we do not believe the oral route to be the ideal route of administration of cannabis for chronic pain.

Transdermal Administration

Transdermal delivery typically utilizes a patch that places an amount of drug in close contact with the skin. The drug is pharmacologically encapsulated in such a manner which allows a small amount to consistently cross the skin and enter the blood plasma for an extended time period.

It produces a blood plasma concentration profile (Figure 4) without any sudden spike or drop in the blood plasma concentration level. Rather, as the cannabinoids slowly seep into the bloodstream the level rises steadily and plateaus within the Therapeutic Range. It stays steady within the range for a prolonged period of time before gradually tapering off.


Transdermal application of cannabinoids much better matches the conditions presented by chronic pain. It never exceeds the Therapeutic Range, thus minimizing psychoactivity, and it stays within this range longer than any other route does, thereby addressing the symptoms for the maximum duration. Additionally, unlike oral administration, it does not undergo first pass metabolism, and thus does not exacerbate the psychoactive effect through elevated levels of 11-OH-THC.

In the opening section of this article we stated that “the ideal blood plasma concentration profile should supply modest amount of cannabinoids, consistently, and for the longest possible duration.” If we compare the three routes presented above, we may conclude that the one offered by transdermal application best approximates this ideal blood plasma concentration profile (Figure 5).


Using a transdermal patch most effectively provides maximum relief from chronic pain symptoms while minimizing the psychoactive effect of cannabis. It is the route we believe is most conducive towards an individual reclaiming their ability to live a normal and healthy life undeterred by pain symptoms and inebriation.




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